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NK1 receptor

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Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 360

Nomenclature: NK1 receptor

Family: Tachykinin receptors

Contents:

Gene and Protein Information Click here for help
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 407 2p12 TACR1 tachykinin receptor 1 43,125
Mouse 7 407 6 C3 Tacr1 tachykinin receptor 1 124
Rat 7 407 4q34 Tacr1 tachykinin receptor 1 58
Previous and Unofficial Names Click here for help
SPR [125] | Substance P receptor | NK1R | TAC1R | neurokinin receptor 1 | NK1 receptor
Database Links Click here for help
Specialist databases
GPCRdb nk1r_human (Hs), nk1r_mouse (Mm), nk1r_rat (Rn)
Other databases
Alphafold P25103 (Hs), P30548 (Mm), P14600 (Rn)
ChEMBL Target CHEMBL249 (Hs), CHEMBL2668 (Mm), CHEMBL4027 (Rn)
DrugBank Target P25103 (Hs)
Ensembl Gene ENSG00000115353 (Hs), ENSMUSG00000030043 (Mm), ENSRNOG00000005853 (Rn)
Entrez Gene 6869 (Hs), 21336 (Mm), 24807 (Rn)
Human Protein Atlas ENSG00000115353 (Hs)
KEGG Gene hsa:6869 (Hs), mmu:21336 (Mm), rno:24807 (Rn)
OMIM 162323 (Hs)
Pharos P25103 (Hs)
RefSeq Nucleotide NM_001058 (Hs), NM_009313 (Mm), NM_012667 (Rn)
RefSeq Protein NP_001049 (Hs), NP_033339 (Mm), NP_036799 (Rn)
UniProtKB P25103 (Hs), P30548 (Mm), P14600 (Rn)
Wikipedia TACR1 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Structure of human NK1 receptor bound to the inhibitor L760735
PDB Id:  6E59
Ligand:  L760735
Resolution:  3.4Å
Species:  Human
References:  143
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the Neurokinin 1 receptor in complex with the small molecule antagonist Netupitant
PDB Id:  6HLP
Ligand:  netupitant
Resolution:  2.2Å
Species:  Human
References:  118
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the Neurokinin 1 receptor in complex with the small molecule antagonist Aprepitant
PDB Id:  6HLO
Ligand:  aprepitant
Resolution:  2.4Å
Species:  Human
References:  118
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the Neurokinin 1 receptor in complex with the small molecule antagonist CP 99994
PDB Id:  6HLL
Ligand:  CP 99994
Resolution:  3.27Å
Species:  Human
References:  118
Natural/Endogenous Ligands Click here for help
hemokinin 1 {Sp: Mouse}
neurokinin A {Sp: Human, Mouse, Rat}
neurokinin B {Sp: Human, Mouse, Rat, Pig}
neuropeptide-γ
neuropeptide K {Sp: Human, Rat}
substance P {Sp: Human, Mouse, Rat}
Comments: Substance P is the highest potency endogenous agonist
Potency order of endogenous ligands (Human)
substance P (TAC1, P20366) > neurokinin A (TAC1, P20366) > neurokinin B (TAC3, Q9UHF0)

Download all structure-activity data for this target as a CSV file go icon to follow link

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[125I]BH-[Sar9,Met(O2)11]SP Peptide Ligand is labelled Ligand is radioactive Rn Full agonist 9.0 pKd 131
⤷ pKd 9.0 (Kd 1x10-9 M) [131]
[3H]BH-[Sar9,Met(O2)11]SP Peptide Ligand is labelled Ligand is radioactive Rn Full agonist 8.7 pKd 132
⤷ pKd 8.7 (Kd 2x10-9 M) [132]
[3H]SP (human, mouse, rat) Peptide Ligand is labelled Ligand is radioactive Hs Full agonist 8.6 pKd 8
⤷ pKd 8.6 (Kd 2.8x10-9 M) [8]
hemokinin 1 {Sp: Mouse} Peptide Click here for species-specific activity table Hs Full agonist 9.8 – 11.7 pKi 12
⤷ pKi 9.8 – 11.7 [12]
substance P {Sp: Human, Mouse, Rat} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 8.5 – 10.3 pKi 12-13
⤷ pKi 8.5 – 10.3 [12-13]
septide Peptide Hs Full agonist 7.0 – 9.3 pKi 12,57
⤷ pKi 7.0 – 9.3 [12,57]
neurokinin A {Sp: Human, Mouse, Rat} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 6.2 – 9.3 pKi 12,44,57,116
⤷ pKi 6.2 – 9.3 [12,44,57,116]
neurokinin B {Sp: Human, Mouse, Rat, Pig} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 6.1 – 6.4 pKi 116
⤷ pKi 6.1 – 6.4 [116]
[Sar9,Met(O2)11]SP Peptide Hs Full agonist 9.7 – 9.9 pIC50 127
⤷ pIC50 9.7 – 9.9 [127]
physalaemin Peptide Hs Full agonist 9.1 – 9.2 pIC50 127
⤷ pIC50 9.1 – 9.2 [127]
eledoisin Peptide Click here for species-specific activity table Hs Full agonist 8.6 pIC50 127
⤷ pIC50 8.6 [127]
[Pro9]SP Peptide Rn Full agonist 8.6 pIC50 130
⤷ pIC50 8.6 (IC50 2.8x10-9 M) [130]
phyllomedusin Peptide Hs Full agonist 8.3 – 8.5 pIC50 127
⤷ pIC50 8.3 – 8.5 [127]
substance P-(4-11) Peptide Hs Full agonist 7.7 – 8.0 pIC50 127
⤷ pIC50 7.7 – 8.0 [127]
neuropeptide-γ Peptide Ligand is endogenous in the given species Hs Full agonist 7.6 – 7.7 pIC50 127
⤷ pIC50 7.6 – 7.7 (IC50 2.82x10-8 – 2.22x10-8 M) [127]
substance P-OMe Peptide Hs Full agonist 7.4 – 7.5 pIC50 127
⤷ pIC50 7.4 – 7.5 [127]
kassinin Peptide Click here for species-specific activity table Hs Full agonist 6.6 – 7.1 pIC50 127
⤷ pIC50 6.6 – 7.1 [127]
neuropeptide K {Sp: Human, Rat} Peptide Ligand is endogenous in the given species Hs Full agonist 6.4 – 6.5 pIC50 127
⤷ pIC50 6.4 – 6.5 [127]
substance P-(6-11) Peptide Hs Full agonist 6.3 – 6.5 pIC50 127
⤷ pIC50 6.3 – 6.5 [127]
[125I]SP (human, mouse, rat) Peptide Ligand is labelled Ligand is radioactive Hs Full agonist - -
⤷
View species-specific agonist tables
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
spantide II Peptide Cp Antagonist 7.0 – 8.1 pA2 38,64
⤷ pA2 7.0 – 8.1 [38,64]
spantide I Peptide Cp Antagonist 7.0 – 7.1 pA2 38,64
⤷ pA2 7.0 – 7.1 [38,64]
[125I]L703,606 Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Antagonist 9.5 pKd 40
⤷ pKd 9.5 (Kd 3x10-10 M) [40]
vofopitant Small molecule or natural product Hs Antagonist 10.6 pKi 41
⤷ pKi 10.6 [41]
T2328 Small molecule or natural product Hs Antagonist 10.1 pKi 140
⤷ pKi 10.1 (Ki 8x10-11 M) [140]
aprepitant Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Hs Antagonist 10.1 pKi 54-55
⤷ pKi 10.1 (Ki 9x10-11 M) [54-55]
lanepitant Small molecule or natural product Hs Antagonist 9.8 – 10.0 pKi 46
⤷ pKi 9.8 – 10.0 (Ki 1.5x10-10 – 1x10-10 M) [46]
ezlopitant Small molecule or natural product Hs Antagonist 9.7 pKi 135
⤷ pKi 9.7 (Ki 2x10-10 M) [135]
CP 99994 Small molecule or natural product Ligand has a PDB structure Hs Antagonist 9.3 – 9.7 pKi 6,116
⤷ pKi 9.3 – 9.7 [6,116]
casopitant Small molecule or natural product Hs Antagonist 9.4 pKi 62,134
⤷ pKi 9.4 [62,134]
vestipitant Small molecule or natural product Hs Antagonist 9.4 pKi 16,33
⤷ pKi 9.4 [16,33]
R116031 Small molecule or natural product Hs Antagonist 9.4 pKi 82
⤷ pKi 9.4 (Ki 4.5x10-10 M) [82]
imnopitant Small molecule or natural product Hs Antagonist 9.2 pKi 61
⤷ pKi 9.2 (Ki 5.8x10-10 M) [61]
rolapitant Small molecule or natural product Approved drug Hs Antagonist 9.2 pKi 34
⤷ pKi 9.2 (Ki 6.6x10-10 M) [34]
FK-888 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 9.1 pKi 65
⤷ pKi 9.1 (Ki 8x10-10 M) [65]
netupitant Small molecule or natural product Approved drug Ligand has a PDB structure Hs Antagonist 9.0 pKi 61
⤷ pKi 9.0 (Ki 9.5x10-10 M) [61]
befetupitant Small molecule or natural product Hs Antagonist 9.0 pKi 61
⤷ pKi 9.0 (Ki 1x10-9 M) [61]
SCH 206272 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.3 – 8.9 pKi 6
⤷ pKi 8.3 – 8.9 [6]
tradipitant Small molecule or natural product Immunopharmacology Ligand Hs Antagonist >7.0 pKi 4
⤷ pKi >7.0 (Ki <1x10-7 M) [4]
Description: Measuring displacement of [125I]-substance P binding to membranes from IM-9 cells (human B lymphocytes)
R-486 Peptide Hs Antagonist 6.5 – 6.6 pKi 6
⤷ pKi 6.5 – 6.6 [6]
saredutant Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.1 – 6.6 pKi 6,116
⤷ pKi 6.1 – 6.6 [6,116]
osanetant Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.0 – 6.6 pKi 6
⤷ pKi 6.0 – 6.6 [6]
spantide I Peptide Rn Antagonist 5.6 pEC50 64
⤷ pEC50 5.6 Inhibition of histamine release from peritoneal mast cells [64]
spantide II Peptide Rn Antagonist 5.5 pEC50 64
⤷ pEC50 5.5 Inhibition of histamine release from peritoneal mast cells. [64]
serlopitant Small molecule or natural product Immunopharmacology Ligand Hs Antagonist 10.2 pIC50 67
⤷ pIC50 10.2 (IC50 6x10-11 M) [67]
Description: Inhibition of binding of 125I-Substance P in vitro.
ZD6021 Small molecule or natural product Hs Antagonist 9.9 pIC50 110
⤷ pIC50 9.9 [110]
lanepitant Small molecule or natural product Hs Antagonist 9.8 pIC50 62
⤷ pIC50 9.8 (IC50 1.5x10-10 M) [62]
L760735 Small molecule or natural product Ligand has a PDB structure Hs Antagonist 9.7 pIC50 56
⤷ pIC50 9.7 (IC50 1.9x10-10 M) [56]
TAK-637 Small molecule or natural product Hs Antagonist 9.4 pIC50 89
⤷ pIC50 9.4 (IC50 4.5x10-10 M) [89]
Description: Inhibition of [125I]BH-SP binding in human IM-9 cells.
nolpitantium Small molecule or natural product Hs Antagonist 8.9 – 9.0 pIC50 127
⤷ pIC50 8.9 – 9.0 [127]
fosaprepitant Small molecule or natural product Approved drug Hs Antagonist 8.9 pIC50 54
⤷ pIC50 8.9 (IC50 1.2x10-9 M) [54]
L-732,138 Small molecule or natural product Primary target of this compound Hs Antagonist 8.6 pIC50 19
⤷ pIC50 8.6 (IC50 2.3x10-9 M) [19]
Description: Antagonism of [125]-substance P binding, to NK1 receptors expressed in CHO cells.
L-703,606 Small molecule or natural product Hs Antagonist 8.2 – 8.4 pIC50 127
⤷ pIC50 8.2 – 8.4 [127]
spantide I Peptide Oc Antagonist 8.3 pIC50 38
⤷ pIC50 8.3 (IC50 5.2x10-9 M) Measuring inhibition of contraction of the rabbit iris sphincter. [38]
spantide II Peptide Oc Antagonist 8.2 pIC50 38
⤷ pIC50 8.2 (IC50 6x10-9 M) Measuring inhibition of contraction of the rabbit iris sphincter. [38]
FK 224 Peptide Click here for species-specific activity table Hs Antagonist 7.5 – 8.3 pIC50 84
⤷ pIC50 7.5 – 8.3 [84]
RP67580 Small molecule or natural product Hs Antagonist 7.7 pIC50 39
⤷ pIC50 7.7 [39]
L-732,138 Small molecule or natural product Rn Antagonist ~6.3 pIC50 19
⤷ pIC50 ~6.3 (IC50 ~4.6x10-7 M) [19]
spantide I Peptide Rn Antagonist 5.7 pIC50 142
⤷ pIC50 5.7 (IC50 2x10-6 M) [142]
osanetant Small molecule or natural product Click here for species-specific activity table Hs Antagonist 5.6 pIC50 11
⤷ pIC50 5.6 [11]
[18F]SPA-RQ Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Antagonist - - 24
⤷ [24]
View species-specific antagonist tables
Antagonist Comments
[126] and [68] both provide evidence indicating that spantide I is an antagonist of the human NK1 receptor.
Immunopharmacology Comments
Expression in monocytes, macrophages and T helper cells suggests a role in inflammation/immunity.
Cell Type Associations
Immuno Cell Type:  T cells
Comment:  T helper cells
References:  29
Immuno Cell Type:  Macrophages & monocytes
Cell Ontology Term:   macrophage (CL:0000235)
monocyte (CL:0000576)
References:  60
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  Cellular signalling
Immuno Process:  Chemotaxis & migration
Immuno Process:  Immune regulation
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gs family
Gq/G11 family 		Adenylyl cyclase stimulation
Phospholipase C stimulation
References:  52,74,78,88,123
Tissue Distribution Click here for help
Bone marrow stroma.
Species:  Human
Technique:  Radioligand binding.
References:  101
Brain cells.
Species:  Human
Technique:  RT-PCR.
References:  79
Colonic epithelial cells.
Species:  Human
Technique:  Western blot.
References:  45
T-Helper cells.
Species:  Human
Technique:  Antagonist effect.
References:  29
Breast cancer cells.
Species:  Human
Technique:  Western blot.
References:  21,96,104
Bone marrow fibroblasts.
Species:  Human
Technique:  Immunocytochemistry.
References:  22
Hematopoietic Progenitors (CD34+).
Species:  Human
Technique:  RT-PCR.
References:  59
Neuroblastoma.
Species:  Human
Technique:  Western blot.
References:  85
Adipose tissue, prostate, pituitary.
Species:  Human
Technique:  in situ hybridisation.
References:  17
Striatum > cerebral cortex, hippocampus, amygdala > thalamus, cerebellum.
Species:  Human
Technique:  in situ hybridisation.
References:  17
Striatum > cerebral cortex.
Species:  Human
Technique:  Autoradiography.
References:  17
Brain; pial surface, mid to upper cortical layers.
Species:  Human
Technique:  Immunohistochemistry.
References:  129
Prefrontal and visual cortex; thin band at the cortical surface and dots of localised on small non-pyramidal cells and in the neuropil (layers I-III).
Species:  Human
Technique:  Immunohistochemistry.
References:  128
Human arterial (umbilical) endothelium.
Species:  Human
Technique:  Autoradiography.
References:  51
Human monocytes and macrophages.
Species:  Human
Technique:  RT-PCR.
References:  60
Intestinal epithelial cells.
Species:  Human
Technique:  Autoradiography.
References:  49
Uterus.
Species:  Mouse
Technique:  Autoradiography.
References:  9
Mouse ileum; interstitial cells of Cajal at the deep muscular plexus, myoid cells of the villi.
Species:  Mouse
Technique:  Immunohistochemistry.
References:  138
Kidney.
Species:  Rat
Technique:  Autoradiography.
References:  23
Gastrointestinal tract.
Species:  Rat
Technique:  Immunohistochemistry.
References:  50
Brainstem auditory nuclei; cochlear nucleus, lateral superior olive, the medial nucleus of the trapezoid body, and inferior colliculus.
Species:  Rat
Technique:  Immunohistochemistry.
References:  53
Superior cervical ganglia.
Species:  Rat
Technique:  Quantitative autoradiography of spontaneously hypertensive rats.
References:  117
Pancreatic acini.
Species:  Rat
Technique:  immunocytochemistry.
References:  15
Tissue Distribution Comments
The NK1 receptor is widely distributed but is increased in malignant cells and appears to facilitate HIV-1 infection. Understanding of the distribution of NK1 subsets (long-form and truncated) on different cancer subsets and the effects on immune cell function are essential for efficient targeting of cancer cells.

NK1 also induces the polarization of T-helper subsets of cells, indicating that specific antagonists could prevent infection and inflammation.
Expression Datasets Click here for help

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays Click here for help
Measurement of cAMP accumulation in COS-7 cells transfected with the human NK1.
Species:  Human
Tissue:  COS-7 cells.
Response measured:  Stimulation of cAMP accumulation.
References:  78
Measurement of IP levels in COS-7 cells transfected with the human NK1 receptor.
Species:  Human
Tissue:  COS-7 cells.
Response measured:  Stimulation of IP turnover.
References:  78
Measurement of interleukin-6 secretion from human astrocytoma cell line U 373 MG endogenously expressing the NK1 receptor.
Species:  Human
Tissue:  U 373 MG cells.
Response measured:  Promotion of secretion of interleukin-6.
References:  47
Measurement of calcium transients in murine colonic myocytes following parallel stimulation of NK1 and NK2.
Species:  Mouse
Tissue:  Colonic myocytes.
Response measured:  Low agonist concentration increases Ca2+ transients. Higher agonist concentration increases basal Ca2+ and inhibits Ca2+ transients.
References:  10
Measurement of IP turnover in rat anterior pituitary membrane cells endogenously expressing NK1.
Species:  Rat
Tissue:  Anterior pituitary membrane.
Response measured:  Stimulation of IP turnover.
References:  80
Measurement of activation of NF-κB in human lung epithelial cells endogenously expressing the NK1 receptor.
Species:  Human
Tissue:  Lung epithelial cells.
Response measured:  NF-κB activation.
References:  141
Induction of tracheal smooth muscle contraction
Species:  Pig
Tissue:  Smooth muscle.
Response measured:  Tracheal contraction.
References:  120
Physiological Functions Click here for help
Release of nitric oxide.
Species:  Human
Tissue:  Endothelium of arterial vessels.
References:  95,109
Measurement of saliva production; saliva accumulated.
Species:  Rat
Tissue:  Submandibular glands.
References:  66
Measurement of saliva production; saliva not accumulated.
Species:  Mouse
Tissue:  Submandibular glands
References:  66
Induction of pressor and tachycardic effects.
Species:  Rat
Tissue: 
References:  137
Exogenous activation induced reinstatement of cocaine-seeking behaviour, but endogenous activity at these receptors was not involved in mediating the priming effects of cocaine on reinstatement of drug-seeking behavior.
Species:  Rat
Tissue:  in vivo
References:  99
Endogenous activity attenuated morhphine-induced locomotor activity and increased heroin self-administration (but had no effect on cocaine-induced locomotor activity or self-administration).
Species:  Rat
Tissue:  in vivo
References:  98
Ganglionic NK1 receptors mediate renal nerve, heart rate and pressor response to Substance P.
Species:  Rat
Tissue:  In vivo (sympathetic ganglia).
References:  117
Initiates micturation reflex.
Species:  Rat
Tissue:  In vivo
References:  75-76,93
Stimulates licking, biting and scratching response.
Species:  Mouse
Tissue:  In vivo
References:  113-115
Mediates plasma extravasation in footpad.
Species:  Rat
Tissue:  In vivo.
References:  5
5-Hydroxytryptamine-induced tracheal contraction includes a cholinergic mechanism that requires the presence of the tachykinin NK(1) receptor.
Species:  Mouse
Tissue:  Trachea
References:  32
Stimulation of behaviour in resident-intruder and forced swim test resembling that seen with the clinically used antidepressent fluoxetine.
Species:  Mouse
Tissue:  In vivo
References:  111
Regulation of severity of acute pancreatitis and pancreatitis-associated lung injury.
Species:  Mouse
Tissue:  In vivo
References:  75
Mediation of substance P-induced edema formation.
Species:  Mouse
Tissue:  In vivo
References:  18
Patients with moderate to severe major depression, robust antidepressant effects were consistently observed upon treatment with and NK1 antagonist.
Species:  Human
Tissue:  In vivo
References:  73
Modulation of nociceptive behaviour induced by intrathecal injection of histamine.
Species:  Mouse
Tissue:  In vivo
References:  144
Intrathecal administration of an NK1 receptor antagonist blocks the colorectal-distension-induced hyperalgesia for both noxious and innocuous stimuli.
Species:  Rat
Tissue:  In vivo.
References:  42
NK1 receptor is required in antigen-induced cystitis.
Species:  Mouse
Tissue:  In vivo
References:  112
Activation of the NK1 receptor modulates vascular tone and permeability in the inflamed joints in knockout mice studies.
Species:  Mouse
Tissue:  In vivo
References:  70
NK1 receptor blockade stimulates the proliferation of neurons in the dentate gyrus suggesting that NK1R blockade may generate anti-depressant-like effects.
Species:  Mouse
Tissue:  In vivo
References:  83
Grooming is induced by the NK1 agonist administered into the substantia nigra.
Species:  Rat
Tissue:  In vivo.
References:  122
Modulation of spontaneous and drug-induced locomotor activity.
Species:  Rat
Tissue:  In vivo.
References:  121
Control of presynaptic dopamine release.
Species:  Rat
Tissue:  In vivo.
References:  48,133
Analgesic effects are induced by NK1 receptor agonists administered to either the ventral tegmental area or nucleus accumbens septi.
Species:  Human
Tissue:  In vivo.
References:  3
Mediates the effect of intravenous tachykinins on vascular permeability in the rat lower urinary tract, through a histamine-independent mechanism.
Species:  Human
Tissue:  Rat lower urinary tract.
References:  1
NK1 receptors are involved in mediating PNV-induced scratching.
Species:  Mouse
Tissue:  In vivo
References:  27
Aprepitant does not reduce the incidence of post-ERCP (endoscopic retrograde cholangiopancreatography) pancreatitis in humans.
Species:  Human
Tissue:  In vivo.
References:  119
NK1 receptor antagonist N-acetyl-L-tryptophan (NAT) improves outcome in female Sprague Dawley rats following diffuse traumatic brain injury.
Species:  Rat
Tissue:  In vivo.
References:  26
NK1 receptor antagonist L-732,138 co-administration attenuates opioid withdrawal-mediated spinal microglia and astrocyte activation in rats.
Species:  Rat
Tissue:  In vivo.
References:  136
Blockade of NK1 receptors with the antagonists L-733,060 and RP-67580 alleviates renal functional and tissue injury in the absence of alteration in blood pressure in DOCA-salt-hypertensive mice.
Species:  Mouse
Tissue:  In vivo.
References:  139
Wound and tissue adhesion
Species:  Rat
Tissue:  In vivo
References:  25,69,107-108
Physiological Consequences of Altering Gene Expression Click here for help
NK1 knockout mice display an abnormal granulomatuous response in Shistosomiasis Mansoni.
Species:  Mouse
Tissue: 
Technique:  Gene knockout.
References:  14
NK1 knockout mice display increased numbers of mast cells in the bladder when compared with the wild type.
Species:  Mouse
Tissue:  Bladder.
Technique:  Gene knockout.
References:  91
NK1 knockout mice displayed decreased induced neutrophil accumulation when treated with interleukin-1β, compared to the wild -type.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells
References:  2
In an intense inflammatory model produced by intra-plantar Mycobacterium tuberculosus, substantial reductions in footpad swelling, histological outcome and mechanical hyperalgesia are observed from early time points in mice lacking the neurokin-1 receptor compared with wild-type controls.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  71
NK1 knockout mice display decreased Phoneutria nigriventer spider venom and substance P-induced oedema formation when compared to the wild-type. NK1 knockout mice display decreased Phoneutria nigriventer spider venom-induced scratching when compared to the wild-type.
Species:  Mouse
Tissue: 
Technique:  Gene tagging in embryonic stem cells
References:  27
In resident-intruder and forced swim tests, NK1 knockout mice display behaviour resembling that seen with the clinically used antidepressent fluoxetine.
Species:  Mouse
Tissue: 
Technique:  Gene tagging in embryonic stem cells
References:  111
NK1 knockout mice shown increased neurogenesis and levels of brain-derived neurotrophic factor in the hippocampus when compared to the wild-type.
Species:  Mouse
Tissue: 
Technique:  Gene tagging in embryonic stem cells
References:  83
Compared to wild type, NK1 knockout mice displayed molecular modifications of signaling pathways involved in the pathophysiology of depression and antidepressant mechanism, such as up-regulation of Ca(2+)-independent enzymatic activity in the prefrontal/frontal cortex, hippocampus and striatum.
Species:  Mouse
Tissue: 
Technique:  Gene tagging in embryonic stem cells
References:  86
NK1 knockout mice display altered nociception, analgesia and aggression compared to the wild-type
Species:  Mouse
Tissue: 
Technique:  Gene tagging in embryonic stem cells
References:  31
The severity of induced pancreatitis in mice lacking the NK1 receptor is decreased compared to the wild=type.
Species:  Mouse
Tissue: 
Technique:  Gene tagging in embryonic stem cells
References:  14
NK1 knockout mice displayed decreased induced neutrophil accumulation when treated with interleukin-1β, compared to the wild -type.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells
References:  2
NK1 knockout mice did not display stress-triggered premature induction of catagen and hair follicle apoptosis, compared to wild type.
Species:  Mouse
Tissue:  Hair follicle.
Technique:  Gene knockout.
References:  7
Disruption of noradrenaline regulation is observed in NK1 knockout mice.
Species:  Human
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  37
NK1 knockout mice are protected from the secretory and inflammatory changes as well as from epithelial cell damage induced by toxin A in the intestine.
Species:  Mouse
Tissue:  Intestine.
Technique:  Gene knock-outs.
References:  20
Substance P causes significant acute plasma extravasation in wild type but not NK1 knockout mice. Complete Freund's adjuvant induced a significant decrease in intravascular volume at early time points in wild type but not NK1 knockout mice. Substance P injection into complete Freund's adjuvant-pretreated joints causes a significant enhancement of plasma extravasation and knee swelling in wild type but not NKNK1 knockout mice.
Species:  Mouse
Tissue: 
Technique:  Gene knockout.
References:  70
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Tacr1tm1Sph Tacr1tm1Sph/Tacr1tm1Sph
involves: 129P2/OlaHsd * C57BL/6		 MGI:98475  MP:0002735 abnormal chemical nociception PMID: 9537323 
Tacr1tm1Nge Tacr1tm1Nge/Tacr1tm1Nge
involves: 129S4/SvJae		 MGI:98475  MP:0001800 abnormal humoral immune response PMID: 8781237 
Tacr1tm1Nge Tacr1tm1Nge/Tacr1tm1Nge
involves: 129S4/SvJae * C57BL		 MGI:98475  MP:0002423 abnormal mast cell physiology PMID: 12867261 
Tacr1tm1Nge Tacr1tm1Nge/Tacr1tm1Nge
involves: 129S4/SvJae		 MGI:98475  MP:0002272 abnormal nervous system electrophysiology PMID: 11465604 
Tacr1tm1Sph Tacr1tm1Sph/Tacr1tm1Sph
involves: 129 * C57BL/6		 MGI:98475  MP:0003633 abnormal nervous system physiology PMID: 10954331 
Tacr1tm1Rhn Tacr1tm1Rhn/Tacr1tm1Rhn
129S/SvEv-Tacr1		 MGI:98475  MP:0004811 abnormal neuron physiology PMID: 11172050 
Tacr1tm1Rhn Tacr1tm1Rhn/Tacr1tm1Rhn
129S/SvEv-Tacr1		 MGI:98475  MP:0002736 abnormal nociception after inflammation PMID: 10718319 
Tacr1tm1Sph Tacr1tm1Sph/Tacr1tm1Sph
involves: 129P2/OlaHsd * C57BL/6		 MGI:98475  MP:0001970 abnormal pain threshold PMID: 9537323 
Tacr1tm1Sph Tacr1tm1Sph/Tacr1tm1Sph
involves: 129P2/OlaHsd		 MGI:98475  MP:0001970 abnormal pain threshold PMID: 11433347 
Tacr1tm1Rhn Tacr1tm1Rhn/Tacr1tm1Rhn
129S/SvEv-Tacr1		 MGI:98475  MP:0008872 abnormal physiological response to xenobiotic PMID: 11172050 
Tacr1tm1Sph Tacr1tm1Sph/Tacr1tm1Sph
involves: 129P2/OlaHsd * C57BL/6		 MGI:98475  MP:0002327 abnormal respiratory function PMID: 12492418 
Tacr1tm1Sph Tacr1tm1Sph/Tacr1tm1Sph
involves: 129P2/OlaHsd * C57BL/6		 MGI:98475  MP:0002281 abnormal respiratory mucosa goblet cell morphology PMID: 15208590 
Tacr1tm1Sph Tacr1tm1Sph/Tacr1tm1Sph
involves: 129P2/OlaHsd * C57BL/6 * MF1		 MGI:98475  MP:0003663 abnormal thermosensation PMID: 15964684 
Tacr1tm1Sph Tacr1tm1Sph/Tacr1tm1Sph
involves: 129P2/OlaHsd * C57BL/6		 MGI:98475  MP:0001968 abnormal touch/ nociception PMID: 9537323 
Tacr1tm1Rhn Tacr1tm1Rhn/Tacr1tm1Rhn
129S/SvEv-Tacr1		 MGI:98475  MP:0001529 abnormal vocalization PMID: 11172050 
Tacr1tm1Sph Tacr1tm1Sph/Tacr1tm1Sph
involves: 129P2/OlaHsd * C57BL/6		 MGI:98475  MP:0005656 decreased aggression PMID: 9537323 
Tacr1tm1Rhn Tacr1tm1Rhn/Tacr1tm1Rhn
129S/SvEv-Tacr1		 MGI:98475  MP:0001364 decreased anxiety-related response PMID: 11172050 
Tacr1tm1Rhn Tacr1tm1Rhn/Tacr1tm1Rhn
129S/SvEv-Tacr1		 MGI:98475  MP:0002665 decreased circulating corticosterone level PMID: 11172050 
Tacr1tm1Sph Tacr1tm1Sph/Tacr1tm1Sph
involves: 129P2/OlaHsd * C57BL/6		 MGI:98475  MP:0001876 decreased inflammatory response PMID: 9537323 
Tacr1tm1Sph Tacr1tm1Sph/Tacr1tm1Sph
involves: 129P2/OlaHsd * C57BL/6		 MGI:98475  MP:0003481 decreased nerve fiber response intensity PMID: 9537323 
Tacr1tm1Nge Tacr1tm1Nge/Tacr1tm1Nge
involves: 129S4/SvJae * C57BL		 MGI:98475  MP:0003071 decreased vascular permeability PMID: 12867261 
Tacr1tm1Sph Tacr1tm1Sph/Tacr1tm1Sph
involves: 129P2/OlaHsd * C57BL/6 * MF1		 MGI:98475  MP:0001399 hyperactivity PMID: 15814105 
Tacr1tm1Sph Tacr1tm1Sph/Tacr1tm1Sph
involves: 129P2/OlaHsd * C57BL/6		 MGI:98475  MP:0005407 hyperalgesia PMID: 14625445 
Tacr1tm1Rhn Tacr1tm1Rhn/Tacr1tm1Rhn
129S/SvEv-Tacr1		 MGI:98475  MP:0005498 hyporesponsive to tactile stimuli PMID: 10718319 
Tacr1tm1Rhn Tacr1tm1Rhn/Tacr1tm1Rhn
129S/SvEv-Tacr1		 MGI:98475  MP:0009747 impaired behavioral response to xenobiotic PMID: 11172050 
Tacr1tm1Sph Tacr1tm1Sph/Tacr1tm1Sph
involves: 129P2/OlaHsd * C57BL/6		 MGI:98475  MP:0001952 increased airway responsiveness PMID: 15208590 
Tacr1tm1Rhn Tacr1tm1Rhn/Tacr1tm1Rhn
129S/SvEv-Tacr1		 MGI:98475  MP:0005533 increased body temperature PMID: 11172050 
Tacr1tm1Rhn Tacr1tm1Rhn/Tacr1tm1Rhn
129S/SvEv-Tacr1		 MGI:98475  MP:0008531 increased chemical nociceptive threshold PMID: 10718319 
Tacr1tm1Sph Tacr1tm1Sph/Tacr1tm1Sph
involves: 129P2/OlaHsd * C57BL/6		 MGI:98475  MP:0002933 joint inflammation PMID: 14625445 
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Breast cancer
Disease Ontology: DOID:1612
OMIM: 114480
References:  63,81,87,90,94,96,100,105-106
Disease:  Colitis
Role:  Colonic inflammation, colonic fibrosis, colitis induced transformation
References:  30,36,45,72,77,92
Disease:  Myelofibrosis
Synonyms: Myelofibrosis with myeloid metaplasia [Orphanet: ORPHA824]
Disease Ontology: DOID:4971
OMIM: 254450
Orphanet: ORPHA824
References:  22,102-103
Clinically-Relevant Mutations and Pathophysiology Comments
The truncated form of neurokinin-1 receptor has been linked to breast cancer. It appears that this short form of neuroninin-1 can induce the induction of the TAC1 gene, resulting in cell autonomous proliferation. It is unclear if the truncated neurokin 1 receptor is involved in the transition of low invasive cancer cells to highly aggressive malignancy. Insights into this question was provided in studies with colitis patients. As the subjects transitioned to malignant transformation, the truncated neurokinin-1 receptor was increased. These studies strongly suggest that targeting the neurokinin-1 receptor could prevent inflammation-induced transformation.
General Comments
In rats subjected to chronic and acute stress or pain, expression of the NK1 receptor in the hippocampus is down-regulated [35]. NK1 expression in pancreatic acinar cells in mice is increased during secratogogue-induced experimental pancreatitis [14]. Respiratory syncytial virus upregulates expression of NK1 in rat lungs [97]. Ablation of NK1-expressing rat spinal neurons with the selective cytotoxin substance P-saporin results in an apparently permanent reduction of thermal hyperalgesia and mechanical allodynia associated with persistent neuropathic and inflammatory pain states [91]. Chronic stimulation of NK1 induces ubiquitination of the receptor, which mediates its degradation and down-regulation [28].

References

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1. Abelli L, Somma V, Maggi CA, Regoli D, Astolfi M, Parlani M, Rovero P, Conte B, Meli A. (1989) Effects of tachykinins and selective tachykinin receptor agonists on vascular permeability in the rat lower urinary tract: evidence for the involvement of NK-1 receptors. J Auton Pharmacol, 9 (4): 253-63. [PMID:2475507]

2. Ahluwalia A, De Felipe C, O'Brien J, Hunt SP, Perretti M. (1998) Impaired IL-1beta-induced neutrophil accumulation in tachykinin NK1 receptor knockout mice. Br J Pharmacol, 124 (6): 1013-5. [PMID:9720767]

3. Altier N, Stewart J. (1997) Tachykinin NK-1 and NK-3 selective agonists induce analgesia in the formalin test for tonic pain following intra-VTA or intra-accumbens microinfusions. Behav Brain Res, 89 (1-2): 151-65. [PMID:9475623]

4. Amegadzie AK, Gardinier KM, Hembre EJ, Hong JE, Jungenheim LN, Muehl BS, Remick DM, Robertson MA, Savin KA. (2003) Triazole derivatives as tachykinin receptor antagonists. Patent number: WO2003091226. Assignee: Eli Lilly And Company. Priority date: 26/04/2002. Publication date: 06/11/2003.

5. Andrews PV, Helme RD, Thomas KL. (1989) NK-1 receptor mediation of neurogenic plasma extravasation in rat skin. Br J Pharmacol, 97 (4): 1232-8. [PMID:2477105]

6. Anthes JC, Chapman RW, Richard C, Eckel S, Corboz M, Hey JA, Fernandez X, Greenfeder S, McLeod R, Sehring S et al.. (2002) SCH 206272: a potent, orally active tachykinin NK(1), NK(2), and NK(3) receptor antagonist. Eur J Pharmacol, 450 (2): 191-202. [PMID:12206858]

7. Arck PC, Handjiski B, Kuhlmei A, Peters EM, Knackstedt M, Peter A, Hunt SP, Klapp BF, Paus R. (2005) Mast cell deficient and neurokinin-1 receptor knockout mice are protected from stress-induced hair growth inhibition. J Mol Med, 83 (5): 386-96. [PMID:15759104]

8. Bahouth SW, Musacchio JM. (1985) Specific binding of [3H]substance P to the rat submaxillary gland. The effects of ions and guanine nucleotides. J Pharmacol Exp Ther, 234 (2): 326-36. [PMID:2410593]

9. Barr AJ, Watson SP, Bernal AL, Nimmo AJ. (1991) The presence of NK3 tachykinin receptors on rat uterus. Eur J Pharmacol, 203 (2): 287-90. [PMID:1724757]

10. Bayguinov O, Hagen B, Sanders KM. (2003) Substance P modulates localized calcium transients and membrane current responses in murine colonic myocytes. Br J Pharmacol, 138 (7): 1233-43. [PMID:12711623]

11. Beaujouan JC, Saffroy M, Torrens Y, Glowinski J. (1997) Potency and selectivity of the tachykinin NK3 receptor antagonist SR 142801. Eur J Pharmacol, 319 (2-3): 307-16. [PMID:9042606]

12. Bellucci F, Carini F, Catalani C, Cucchi P, Lecci A, Meini S, Patacchini R, Quartara L, Ricci R, Tramontana M et al.. (2002) Pharmacological profile of the novel mammalian tachykinin, hemokinin 1. Br J Pharmacol, 135 (1): 266-74. [PMID:11786503]

13. Bennacef I, Tymciu S, Dhilly M, Lasne MC, Debruyne D, Perrio C, Barré L. (2004) Synthesis and biological evaluation of novel fluoro and iodo quinoline carboxamides as potential ligands of NK-3 receptors for in vivo imaging studies. Bioorg Med Chem, 12 (16): 4533-41. [PMID:15265501]

14. Blum AM, Metwali A, Kim-Miller M, Li J, Qadir K, Elliott DE, Lu B, Fabry Z, Gerard N, Weinstock JV. (1999) The substance P receptor is necessary for a normal granulomatous response in murine schistosomiasis mansoni. J Immunol, 162 (10): 6080-5. [PMID:10229849]

15. Broccardo M, Ciotti MT, Linari G, Agostini S, Petrella C, Amadoro G, Severini C, Improta G. (2005) Immunocytochemical distribution of NK-1 and NK-3 tachykinin receptors in isolated pancreatic acini of guinea pigs and rats. Peptides, 26 (11): 2351-4. [PMID:15970359]

16. Brocco M, Dekeyne A, Mannoury la Cour C, Touzard M, Girardon S, Veiga S, de Nanteuil G, deJong TR, Olivier B, Millan MJ. (2008) Cellular and behavioural profile of the novel, selective neurokinin1 receptor antagonist, vestipitant: a comparison to other agents. Eur Neuropsychopharmacol, 18 (10): 729-50. [PMID:18657401]

17. Caberlotto L, Hurd YL, Murdock P, Wahlin JP, Melotto S, Corsi M, Carletti R. (2003) Neurokinin 1 receptor and relative abundance of the short and long isoforms in the human brain. Eur J Neurosci, 17: 1736-1746. [PMID:12752772]

18. Cao T, Gerard NP, Brain SD. (1999) Use of NK(1) knockout mice to analyze substance P-induced edema formation. Am J Physiol, 277 (2): R476-81. [PMID:10444554]

19. Cascieri MA, Macleod AM, Underwood D, Shiao LL, Ber E, Sadowski S, Yu H, Merchant KJ, Swain CJ, Strader CD et al.. (1994) Characterization of the interaction of N-acyl-L-tryptophan benzyl ester neurokinin antagonists with the human neurokinin-1 receptor. J Biol Chem, 269 (9): 6587-91. [PMID:7509807]

20. Castagliuolo I, Riegler M, Pasha A, Nikulasson S, Lu B, Gerard C, Gerard NP, Pothoulakis C. (1998) Neurokinin-1 (NK-1) receptor is required in Clostridium difficile- induced enteritis. J Clin Invest, 101 (8): 1547-50. [PMID:9541482]

21. Castro TA, Cohen MC, Rameshwar P. (2005) The expression of neurokinin-1 and preprotachykinin-1 in breast cancer cells depends on the relative degree of invasive and metastatic potential. Clin Exp Metastasis, 22 (8): 621-8. [PMID:16642400]

22. Chang VT, Yook C, Rameshwar P. (2013) Synergism between fibronectin and transforming growth factor-β1 in the production of substance P in monocytes of patients with myelofibrosis. Leuk Lymphoma, 54 (3): 631-8. [PMID:22906243]

23. Chen Y, Hoover DB. (1995) Autoradiographic localization of NK1 and NK3 tachykinin receptors in rat kidney. Peptides, 16 (4): 673-81. [PMID:7479302]

24. Chin FT, Morse CL, Shetty HU, Pike VW. (2006) Automated radiosynthesis of [18F]SPA-RQ for imaging human brain NK1 receptors with PET. J Label Comp Radiopharm, (49): 17-31.

25. Cohen PA, Gower AC, Stucchi AF, Leeman SE, Becker JM, Reed KL. (2007) A neurokinin-1 receptor antagonist that reduces intraabdominal adhesion formation increases peritoneal matrix metalloproteinase activity. Wound Repair Regen, 15 (6): 800-8. [PMID:18028127]

26. Corrigan F, Leonard A, Ghabriel M, Van Den Heuvel C, Vink R. (2012) A substance P antagonist improves outcome in female Sprague Dawley rats following diffuse traumatic brain injury. CNS Neurosci Ther, 18 (6): 513-5. [PMID:22672307]

27. Costa SK, Starr A, Hyslop S, Gilmore D, Brain SD. (2006) How important are NK(1) receptors for influencing microvascular inflammation and itch in the skin? Studies using Phoneutria nigriventer venom. Vascul Pharmacol, 45: 209-214. [PMID:16914387]

28. Cottrell GS, Padilla B, Pikios S, Roosterman D, Steinhoff M, Gehringer D, Grady EF, Bunnett NW. (2006) Ubiquitin-dependent down-regulation of the neurokinin-1 receptor. J Biol Chem, 281 (38): 27773-83. [PMID:16849335]

29. Cunin P, Caillon A, Corvaisier M, Garo E, Scotet M, Blanchard S, Delneste Y, Jeannin P. (2011) The tachykinins substance P and hemokinin-1 favor the generation of human memory Th17 cells by inducing IL-1β, IL-23, and TNF-like 1A expression by monocytes. J Immunol, 186 (7): 4175-82. [PMID:21368235]

30. Dai L, Perera DS, King DW, Southwell BR, Burcher E, Liu L. (2012) Hemokinin-1 stimulates prostaglandin E₂ production in human colon through activation of cyclooxygenase-2 and inhibition of 15-hydroxyprostaglandin dehydrogenase. J Pharmacol Exp Ther, 340 (1): 27-36. [PMID:21957267]

31. De Felipe C, Herrero JF, O'Brien JA, Palmer JA, Doyle CA, Smith AJ, Laird JM, Belmonte C, Cervero F, Hunt SP. (1998) Altered nociception, analgesia and aggression in mice lacking the receptor for substance P. Nature, 392 (6674): 394-7. [PMID:9537323]

32. De Swert KO, Lefebvre RA, Pauwels RA, Joos GF. (2007) Role of the tachykinin NK(1) receptor in mediating contraction to 5-hydroxytryptamine and antigen in the mouse trachea. Pulm Pharmacol Ther, 20 (5): 588-95. [PMID:16919985]

33. Di Fabio R, Griffante C, Alvaro G, Pentassuglia G, Pizzi DA, Donati D, Rossi T, Guercio G, Mattioli M, Cimarosti Z et al.. (2009) Discovery process and pharmacological characterization of 2-(S)-(4-fluoro-2-methylphenyl)piperazine-1-carboxylic acid [1-(R)-(3,5-bis-trifluoromethylphenyl)ethyl]methylamide (vestipitant) as a potent, selective, and orally active NK1 receptor antagonist. J Med Chem, 52 (10): 3238-47. [PMID:19388677]

34. Duffy RA, Morgan C, Naylor R, Higgins GA, Varty GB, Lachowicz JE, Parker EM. (2012) Rolapitant (SCH 619734): a potent, selective and orally active neurokinin NK1 receptor antagonist with centrally-mediated antiemetic effects in ferrets. Pharmacol Biochem Behav, 102 (1): 95-100. [PMID:22497992]

35. Duric V, McCarson KE. (2005) Hippocampal neurokinin-1 receptor and brain-derived neurotrophic factor gene expression is decreased in rat models of pain and stress. Neuroscience, 133: 999-1006. [PMID:15964488]

36. Engel MA, Becker C, Reeh PW, Neurath MF. (2011) Role of sensory neurons in colitis: increasing evidence for a neuroimmune link in the gut. Inflamm Bowel Dis, 17 (4): 1030-3. [PMID:20722067]

37. Fisher AS, Stewart RJ, Yan T, Hunt SP, Stanford SC. (2007) Disruption of noradrenergic transmission and the behavioural response to a novel environment in NK1R-/- mice. Eur J Neurosci, 25 (4): 1195-204. [PMID:17331215]

38. Folkers K, Feng DM, Asano N, Håkanson R, Weisenfeld-Hallin Z, Leander S. (1990) Spantide II, an effective tachykinin antagonist having high potency and negligible neurotoxicity. Proc Natl Acad Sci USA, 87 (12): 4833-5. [PMID:1693780]

39. Fong TM, Yu H, Strader CD. (1992) Molecular basis for the species selectivity of the neurokinin-1 receptor antagonists CP-96,345 and RP67580. J Biol Chem, 267 (36): 25668-71. [PMID:1281470]

40. Francis BE, Swain C, Sabin V, Burns HD. (1994) Radioiodinated L-703,606: a potent, selective antagonist to the human NK1 receptor. Appl Radiat Isot, 45 (1): 97-103. [PMID:8287060]

41. Gardner CJ, Armour DR, Beattie DT, Gale JD, Hawcock AB, Kilpatrick GJ, Twissell DJ, Ward P. (1996) GR205171: a novel antagonist with high affinity for the tachykinin NK1 receptor, and potent broad-spectrum anti-emetic activity. Regul Pept, 65 (1): 45-53. [PMID:8876035]

42. Gaudreau GA, Plourde V. (2003) Role of tachykinin NK1, NK2 and NK3 receptors in the modulation of visceral hypersensitivity in the rat. Neurosci Lett, 351 (2): 59-62. [PMID:14583381]

43. Gerard NP, Garraway LA, Eddy Jr RL, Shows TB, Iijima H, Paquet JL, Gerard C. (1991) Human substance P receptor (NK-1): organization of the gene, chromosome localization, and functional expression of cDNA clones. Biochemistry, 30 (44): 10640-6. [PMID:1657150]

44. Gether U, Marray T, Schwartz TW, Johansen TE. (1992) Stable expression of high affinity NK1 (substance P) and NK2 (neurokinin A) receptors but low affinity NK3 (neurokinin B) receptors in transfected CHO cells. FEBS Lett, 296 (3): 241-4. [PMID:1311270]

45. Gillespie E, Leeman SE, Watts LA, Coukos JA, O'Brien MJ, Cerda SR, Farraye FA, Stucchi AF, Becker JM. (2011) Truncated neurokinin-1 receptor is increased in colonic epithelial cells from patients with colitis-associated cancer. Proc Natl Acad Sci USA, 108 (42): 17420-5. [PMID:21969570]

46. Gitter BD, Bruns RF, Howbert JJ, Waters DC, Threlkeld PG, Cox LM, Nixon JA, Lobb KL, Mason NR, Stengel PW. (1995) Pharmacological characterization of LY303870: a novel, potent and selective nonpeptide substance P (neurokinin-1) receptor antagonist. J Pharmacol Exp Ther, 275 (2): 737-44. [PMID:7473161]

47. Gitter BD, Regoli D, Howbert JJ, Glasebrook AL, Waters DC. (1994) Interleukin-6 secretion from human astrocytoma cells induced by substance P. J Neuroimmunol, 51 (1): 101-8. [PMID:7512575]

48. Glowinski J, Kemel ML, Desban M, Gauchy C, Lavielle S, Chassaing G, Beaujouan JC, Tremblay L. (1993) Distinct presynaptic control of dopamine release in striosomal- and matrix-enriched areas of the rat striatum by selective agonists of NK1, NK2 and NK3 tachykinin receptors. Regul Pept, 46 (1-2): 124-8. [PMID:7692480]

49. Goode T, O'Connell J, Anton P, Wong H, Reeve J, O'Sullivan GC, Collins JK, Shanahan F. (2000) Neurokinin-1 receptor expression in inflammatory bowel disease: molecular quantitation and localisation. Gut, 47 (3): 387-96. [PMID:10940277]

50. Grady EF, Baluk P, Böhm S, Gamp PD, Wong H, Payan DG, Ansel J, Portbury AL, Furness JB, McDonald DM et al.. (1996) Characterization of antisera specific to NK1, NK2, and NK3 neurokinin receptors and their utilization to localize receptors in the rat gastrointestinal tract. J Neurosci, 16 (21): 6975-86. [PMID:8824334]

51. Greeno EW, Mantyh P, Vercellotti GM, Moldow CF. (1993) Functional neurokinin 1 receptors for substance P are expressed by human vascular endothelium. J Exp Med, 177 (5): 1269-76. [PMID:7683033]

52. Guard S, Watson SP. (1991) Tachykinin receptor types: Classification and membrane signalling mechanisms. Neurochem Int, 18 (2): 149-65. [PMID:20504688]

53. Hafidi A, Beurg M, Bouleau Y, Dulon D. (2002) Comparative distribution of NK1, NK2, and NK3 receptors in the rat brainstem auditory nuclei. Brain Res, 947 (2): 299-306. [PMID:12176174]

54. Hale JJ, Mills SG, MacCoss M, Dorn CP, Finke PE, Budhu RJ, Reamer RA, Huskey SE, Luffer-Atlas D, Dean BJ et al.. (2000) Phosphorylated morpholine acetal human neurokinin-1 receptor antagonists as water-soluble prodrugs. J Med Chem, 43 (6): 1234-41. [PMID:10737756]

55. Hale JJ, Mills SG, MacCoss M, Finke PE, Cascieri MA, Sadowski S, Ber E, Chicchi GG, Kurtz M, Metzger J et al.. (1998) Structural optimization affording 2-(R)-(1-(R)-3, 5-bis(trifluoromethyl)phenylethoxy)-3-(S)-(4-fluoro)phenyl-4- (3-oxo-1,2,4-triazol-5-yl)methylmorpholine, a potent, orally active, long-acting morpholine acetal human NK-1 receptor antagonist. J Med Chem, 41 (23): 4607-14. [PMID:9804700]

56. Harrison T, Owens AP, Williams BJ, Swain CJ, Williams A, Carlson EJ, Rycroft W, Tattersall FD, Cascieri MA, Chicchi GG et al.. (2001) An orally active, water-soluble neurokinin-1 receptor antagonist suitable for both intravenous and oral clinical administration. J Med Chem, 44 (24): 4296-9. [PMID:11708932]

57. Hastrup H, Schwartz TW. (1996) Septide and neurokinin A are high-affinity ligands on the NK-1 receptor: evidence from homologous versus heterologous binding analysis. FEBS Lett, 399: 264-266. [PMID:8985159]

58. Hershey AD, Dykema PE, Krause JE. (1991) Organization, structure, and expression of the gene encoding the rat substance P receptor. J Biol Chem, 266 (7): 4366-74. [PMID:1705552]

59. Hiramoto M, Aizawa S, Iwase O, Nakano M, Toyama K, Hoque M, Nabeshima R, Kaidow A, Imai T, Hoshi H et al.. (1998) Stimulatory effects of substance P on CD34 positive cell proliferation and differentiation in vitro are mediated by the modulation of stromal cell function. Int J Mol Med, 1 (2): 347-54. [PMID:9852236]

60. Ho WZ, Lai JP, Zhu XH, Uvaydova M, Douglas SD. (1997) Human monocytes and macrophages express substance P and neurokinin-1 receptor. J Immunol, 159 (11): 5654-60. [PMID:9548509]

61. Hoffmann T, Bös M, Stadler H, Schnider P, Hunkeler W, Godel T, Galley G, Ballard TM, Higgins GA, Poli SM et al.. (2006) Design and synthesis of a novel, achiral class of highly potent and selective, orally active neurokinin-1 receptor antagonists. Bioorg Med Chem Lett, 16 (5): 1362-5. [PMID:16332435]

62. Huang SC, Korlipara VL. (2010) Neurokinin-1 receptor antagonists: a comprehensive patent survey. Expert Opin Ther Pat, 20 (8): 1019-45. [PMID:20533894]

63. Huang WQ, Wang JG, Chen L, Wei HJ, Chen H. (2010) SR140333 counteracts NK-1 mediated cell proliferation in human breast cancer cell line T47D. J Exp Clin Cancer Res, 29: 55. [PMID:20497542]

64. Håkanson R, Leander S, Asano N, Feng DM, Folkers K. (1990) Spantide II, a novel tachykinin antagonist having high potency and low histamine-releasing effect. Regul Pept, 31 (1): 75-82. [PMID:1702895]

65. Ichinose M, Miura M, Yamauchi H, Kageyama N, Tomaki M, Oyake T, Ohuchi Y, Hida W, Miki H, Tamura G et al.. (1996) A neurokinin 1-receptor antagonist improves exercise-induced airway narrowing in asthmatic patients. Am J Respir Crit Care Med, 153 (3): 936-41. [PMID:8630576]

66. Iwabuchi Y, Aoki C, Masuhara T. (1989) Effects of tachykinins on the secretion of fluid and glycoproteins from the submandibular glands of rat, mouse, hamster and guinea pig. Jpn J Pharmacol, 51 (3): 428-31. [PMID:2482911]

67. Jiang J, Bunda JL, Doss GA, Chicchi GG, Kurtz MM, Tsao KL, Tong X, Zheng S, Upthagrove A, Samuel K et al.. (2009) Potent, brain-penetrant, hydroisoindoline-based human neurokinin-1 receptor antagonists. J Med Chem, 52 (9): 3039-46. [PMID:19354254]

68. Johnson BJ, Brubaker JR, Roehrig JT, Trent DW. (1990) Variants of Venezuelan equine encephalitis virus that resist neutralization define a domain of the E2 glycoprotein. Virology, 177 (2): 676-83. [PMID:1695412]

69. Katayama I, Nishioka K. (1997) Substance P augments fibrogenic cytokine-induced fibroblast proliferation: possible involvement of neuropeptide in tissue fibrosis. J Dermatol Sci, 15 (3): 201-6. [PMID:9302648]

70. Keeble J, Blades M, Pitzalis C, Castro da Rocha FA, Brain SD. (2005) The role of substance P in microvascular responses in murine joint inflammation. Br J Pharmacol, 144 (8): 1059-66. [PMID:15700029]

71. Kidd BL, Inglis JJ, Vetsika K, Hood VC, De Felipe C, Bester H, Hunt SP, Cruwys SC. (2003) Inhibition of inflammation and hyperalgesia in NK-1 receptor knock-out mice. Neuroreport, 14 (17): 2189-92. [PMID:14625445]

72. Koon HW, Shih D, Karagiannides I, Zhao D, Fazelbhoy Z, Hing T, Xu H, Lu B, Gerard N, Pothoulakis C. (2010) Substance P modulates colitis-associated fibrosis. Am J Pathol, 177 (5): 2300-9. [PMID:20889569]

73. Kramer MS, Cutler N, Feighner J, Shrivastava R, Carman J, Sramek JJ, Reines SA, Liu G, Snavely D, Wyatt-Knowles E et al.. (1998) Distinct mechanism for antidepressant activity by blockade of central substance P receptors. Science, 281 (5383): 1640-5. [PMID:9733503]

74. Laniyonu A, Sliwinski-Lis E, Fleming N. (1988) Different tachykinin receptor subtypes are coupled to the phosphoinositide or cyclic AMP signal transduction pathways in rat submandibular cells. FEBS Lett, 240 (1-2): 186-90. [PMID:2461321]

75. Lecci A, Giuliani S, Maggi CA. (1992) Effect of the NK-1 receptor antagonist GR 82,334 on reflexly-induced bladder contractions. Life Sci, 51 (26): PL277-80. [PMID:1335533]

76. Lecci A, Giuliani S, Patacchini R, Maggi CA. (1993) Evidence against a peripheral role of tachykinins in the initiation of micturition reflex in rats. J Pharmacol Exp Ther, 264: 1327-1332. [PMID:8383746]

77. Liu L, Markus I, Saghire HE, Perera DS, King DW, Burcher E. (2011) Distinct differences in tachykinin gene expression in ulcerative colitis, Crohn's disease and diverticular disease: a role for hemokinin-1?. Neurogastroenterol Motil, 23 (5): 475-83, e179-80. [PMID:21342363]

78. Martini L, Hastrup H, Holst B, Fraile-Ramos A, Marsh M, Schwartz TW. (2002) NK1 receptor fused to beta-arrestin displays a single-component, high-affinity molecular phenotype. Mol Pharmacol, 62 (1): 30-7. [PMID:12065752]

79. Massillon D, Chen W, Hawkins M, Liu R, Barzilai N, Rossetti L. (1995) Quantitation of hepatic glucose fluxes and pathways of hepatic glycogen synthesis in conscious mice. Am J Physiol, 269 (6 Pt 1): E1037-43. [PMID:8572194]

80. Mau SE, Larsen PJ, Mikkelsen JA, Saermark T. (1990) Substance P and related tachykinins induce receptor-mediated hydrolysis of polyphosphoinositides in the rat anterior pituitary. Mol Cell Endocrinol, 69 (1): 69-78. [PMID:1691115]

81. Mayordomo C, García-Recio S, Ametller E, Fernández-Nogueira P, Pastor-Arroyo EM, Vinyals L, Casas I, Gascón P, Almendro V. (2012) Targeting of substance P induces cancer cell death and decreases the steady state of EGFR and Her2. J Cell Physiol, 227 (4): 1358-66. [PMID:21604273]

82. Megens AA, Ashton D, Vermeire JC, Vermote PC, Hens KA, Hillen LC, Fransen JF, Mahieu M, Heylen L, Leysen JE et al.. (2002) Pharmacological profile of (2R-trans)-4-[1-[3,5-bis(trifluoromethyl)benzoyl]-2-(phenylmethyl)-4-piperidinyl]-N-(2,6-dimethylphenyl)-1-acetamide (S)-Hydroxybutanedioate (R116301), an orally and centrally active neurokinin-1 receptor antagonist. J Pharmacol Exp Ther, 302 (2): 696-709. [PMID:12130734]

83. Morcuende S, Gadd CA, Peters M, Moss A, Harris EA, Sheasby A, Fisher AS, De Felipe C, Mantyh PW, Rupniak NM et al.. (2003) Increased neurogenesis and brain-derived neurotrophic factor in neurokinin-1 receptor gene knockout mice. Eur J Neurosci, 18 (7): 1828-36. [PMID:14622216]

84. Morimoto H, Murai M, Maeda Y, Yamaoka M, Nishikawa M, Kiyotoh S, Fujii T. (1992) FK 224, a novel cyclopeptide substance P antagonist with NK1 and NK2 receptor selectivity. J Pharmacol Exp Ther, 262 (1): 398-402. [PMID:1378096]

85. Mukerji I, Ramkissoon SH, Reddy KK, Rameshwar P. (2005) Autocrine proliferation of neuroblastoma cells is partly mediated through neurokinin receptors: relevance to bone marrow metastasis. J Neurooncol, 71 (2): 91-8. [PMID:15690122]

86. Musazzi L, Perez J, Hunt SP, Racagni G, Popoli M. (2005) Changes in signaling pathways regulating neuroplasticity induced by neurokinin 1 receptor knockout. Eur J Neurosci, 21 (5): 1370-8. [PMID:15813946]

87. Muñoz M, Rosso M, Casinello F, Coveñas R. (2010) Paravertebral anesthesia: how substance P and the NK-1 receptor could be involved in regional block and breast cancer recurrence. Breast Cancer Res Treat, 122 (2): 601-3. [PMID:20333544]

88. Nakajima Y, Tsuchida K, Negishi M, Ito S, Nakanishi S. (1992) Direct linkage of three tachykinin receptors to stimulation of both phosphatidylinositol hydrolysis and cyclic AMP cascades in transfected Chinese hamster ovary cells. J Biol Chem, 267 (4): 2437-42. [PMID:1370820]

89. Natsugari H, Ikeura Y, Kamo I, Ishimaru T, Ishichi Y, Fujishima A, Tanaka T, Kasahara F, Kawada M, Doi T. (1999) Axially chiral 1,7-naphthyridine-6-carboxamide derivatives as orally active tachykinin NK(1) receptor antagonists: synthesis, antagonistic activity, and effects on bladder functions. J Med Chem, 42 (19): 3982-93. [PMID:10508446]

90. Navarro P, Ramkissoon SH, Shah S, Park JM, Murthy RG, Patel SA, Greco SJ, Rameshwar P. (2012) An indirect role for the oncomir-519b in the expression of truncated neurokinin-1 in breast cancer cells. Exp Cell Res, 318 (20): 2604-15. [PMID:22981979]

91. Nichols ML, Allen BJ, Rogers SD, Ghilardi JR, Honore P, Luger NM, Finke MP, Li J, Lappi DA, Simone DA et al.. (1999) Transmission of chronic nociception by spinal neurons expressing the substance P receptor. Science, 286 (5444): 1558-61. [PMID:10567262]

92. Pagán B, Isidro AA, Coppola D, Chen Z, Ren Y, Wu J, Appleyard CB. (2010) Effect of a neurokinin-1 receptor antagonist in a rat model of colitis-associated colon cancer. Anticancer Res, 30 (9): 3345-53. [PMID:20944107]

93. Palea S, Dalforno G, Gaviraghi G, Hagan RM, Trist DG, Pietra C. (1993) Further studies on the effects of selective neurokinin agonists upon the activation of micturition reflex in rats. Evidence for a dual NK-1 receptor mediated excitatory and inhibitory activity. Neuropeptides, 24 (5): 285-91. [PMID:7687043]

94. Palma C. (2006) Tachykinins and their receptors in human malignancies. Curr Drug Targets, 7 (8): 1043-52. [PMID:16918332]

95. Palmer RM, Ferrige AG, Moncada S. (1987) Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature, 327 (6122): 524-6. [PMID:3495737]

96. Patel HJ, Ramkissoon SH, Patel PS, Rameshwar P. (2005) Transformation of breast cells by truncated neurokinin-1 receptor is secondary to activation by preprotachykinin-A peptides. Proc Natl Acad Sci USA, 102 (48): 17436-41. [PMID:16291810]

97. Piedimonte G, Rodriguez MM, King KA, McLean S, Jiang X. (1999) Respiratory syncytial virus upregulates expression of the substance P receptor in rat lungs. Am J Physiol, 277 (4): L831-40. [PMID:10516226]

98. Placenza FM, Fletcher PJ, Vaccarino FJ, Erb S. (2006) Effects of central neurokinin-1 receptor antagonism on cocaine- and opiate-induced locomotor activity and self-administration behaviour in rats. Pharmacol Biochem Behav, 84 (1): 94-101. [PMID:16757018]

99. Placenza FM, Vaccarino FJ, Fletcher PJ, Erb S. (2005) Activation of central neurokinin-1 receptors induces reinstatement of cocaine-seeking behavior. Neurosci Lett, 390: 42-47. [PMID:16125318]

100. Rameshwar P. (2007) Implication of possible therapies targeted for the tachykinergic system with the biology of neurokinin receptors and emerging related proteins. Recent Pat CNS Drug Discov, 2 (1): 79-84. [PMID:18221219]

101. Rameshwar P, Gascón P. (1995) Substance P (SP) mediates production of stem cell factor and interleukin-1 in bone marrow stroma: potential autoregulatory role for these cytokines in SP receptor expression and induction. Blood, 86 (2): 482-90. [PMID:7541664]

102. Rameshwar P, Joshi DD, Yadav P, Qian J, Gascon P, Chang VT, Anjaria D, Harrison JS, Song X. (2001) Mimicry between neurokinin-1 and fibronectin may explain the transport and stability of increased substance P immunoreactivity in patients with bone marrow fibrosis. Blood, 97 (10): 3025-31. [PMID:11342427]

103. Rameshwar P, Oh HS, Yook C, Gascon P, Chang VT. (2003) Substance p-fibronectin-cytokine interactions in myeloproliferative disorders with bone marrow fibrosis. Acta Haematol, 109 (1): 1-10. [PMID:12486316]

104. Ramkissoon SH, Patel PS, Taborga M, Rameshwar P. (2007) Nuclear factor-kappaB is central to the expression of truncated neurokinin-1 receptor in breast cancer: implication for breast cancer cell quiescence within bone marrow stroma. Cancer Res, 67 (4): 1653-9. [PMID:17308106]

105. Reddy BY, Greco SJ, Patel PS, Trzaska KA, Rameshwar P. (2009) RE-1-silencing transcription factor shows tumor-suppressor functions and negatively regulates the oncogenic TAC1 in breast cancer cells. Proc Natl Acad Sci USA, 106 (11): 4408-13. [PMID:19246391]

106. Reddy BY, Trzaska KA, Murthy RG, Navarro P, Rameshwar P. (2008) Neurokinin receptors as potential targets in breast cancer treatment. Curr Drug Discov Technol, 5 (1): 15-9. [PMID:18537563]

107. Reed KL, Fruin AB, Bishop-Bartolomei KK, Gower AC, Nicolaou M, Stucchi AF, Leeman SE, Becker JM. (2002) Neurokinin-1 receptor and substance P messenger RNA levels increase during intraabdominal adhesion formation. J Surg Res, 108 (1): 165-72. [PMID:12443729]

108. Reed KL, Fruin AB, Gower AC, Stucchi AF, Leeman SE, Becker JM. (2004) A neurokinin 1 receptor antagonist decreases postoperative peritoneal adhesion formation and increases peritoneal fibrinolytic activity. Proc Natl Acad Sci USA, 101 (24): 9115-20. [PMID:15187234]

109. Regoli D, Boudon A, Fauchére JL. (1994) Receptors and antagonists for substance P and related peptides. Pharmacol Rev, 46 (4): 551-99. [PMID:7534932]

110. Rumsey WL, Aharony D, Bialecki RA, Abbott BM, Barthlow HG, Caccese R, Ghanekar S, Lengel D, McCarthy M, Wenrich B et al.. (2001) Pharmacological characterization of ZD6021: a novel, orally active antagonist of the tachykinin receptors. J Pharmacol Exp Ther, 298 (1): 307-15. [PMID:11408556]

111. Rupniak NM, Carlson EJ, Webb JK, Harrison T, Porsolt RD, Roux S, de Felipe C, Hunt SP, Oates B, Wheeldon A. (2001) Comparison of the phenotype of NK1R-/- mice with pharmacological blockade of the substance P (NK1 ) receptor in assays for antidepressant and anxiolytic drugs. Behav Pharmacol, 12 (6-7): 497-508. [PMID:11742144]

112. Saban R, Saban MR, Nguyen NB, Lu B, Gerard C, Gerard NP, Hammond TG. (2000) Neurokinin-1 (NK-1) receptor is required in antigen-induced cystitis. Am J Pathol, 156 (3): 775-80. [PMID:10702392]

113. Sakurada T, Tan-No K, Yamada T, Sakurada S, Kisara K, Ohba M, Terenius L. (1990) N-terminal substance P fragments inhibit the spinally induced, NK 1 receptor mediated behavioural responses in mice. Life Sci, 47 (20): PL109-13. [PMID:1701844]

114. Sakurada T, Yamada T, Sakurada S, Kisara K, Ohba M. (1989) Substance P analogues containing D-histidine antagonize the behavioural effects of intrathecally co-administered substance P in mice. Eur J Pharmacol, 174 (2-3): 153-60. [PMID:2483548]

115. Sakurada T, Yamada T, Tan-no K, Manome Y, Sakurada S, Kisara K, Ohba M. (1991) Differential effects of substance P analogs on neurokinin 1 receptor agonists in the mouse spinal cord. J Pharmacol Exp Ther, 259: 205-210. [PMID:1717679]

116. Sarau HM, Griswold DE, Potts W, Foley JJ, Schmidt DB, Webb EF, Martin LD, Brawner ME, Elshourbagy NA, Medhurst AD et al.. (1997) Nonpeptide tachykinin receptor antagonists: I. Pharmacological and pharmacokinetic characterization of SB 223412, a novel, potent and selective neurokinin-3 receptor antagonist. J Pharmacol Exp Ther, 281 (3): 1303-11. [PMID:9190866]

117. Schoborg RV, Hoover DB, Tompkins JD, Hancock JC. (2000) Increased ganglionic responses to substance P in hypertensive rats due to upregulation of NK(1) receptors. Am J Physiol Regul Integr Comp Physiol, 279 (5): R1685-94. [PMID:11049850]

118. Schöppe J, Ehrenmann J, Klenk C, Rucktooa P, Schütz M, Doré AS, Plückthun A. (2019) Crystal structures of the human neurokinin 1 receptor in complex with clinically used antagonists. Nat Commun, 10 (1): 17. [PMID:30604743]

119. Shah TU, Liddle R, Branch MS, Jowell P, Obando J, Poleski M. (2012) Pilot study of aprepitant for prevention of post-ERCP pancreatitis in high risk patients: a phase II randomized, double-blind placebo controlled trial. JOP, 13 (5): 514-8. [PMID:22964958]

120. Sheldrick RL, Ball DI, Coleman RA. (1990) Characterisation of the neurokinin receptors mediating contraction of isolated tracheal preparations from a variety of species. Agents Actions Suppl, 31: 205-9. [PMID:1706905]

121. Stoessl AJ, Dourish CT, Iversen SD. (1988) The NK-3 tachykinin receptor agonist senktide elicits 5-HT-mediated behaviour following central or peripheral administration in mice and rats. Br J Pharmacol, 94 (2): 285-7. [PMID:2456111]

122. Stoessl AJ, Szczutkowski E, Glenn B, Watson I. (1991) Behavioural effects of selective tachykinin agonists in midbrain dopamine regions. Brain Res, 565 (2): 254-62. [PMID:1668812]

123. Stratowa C, Machat H, Burger E, Himmler A, Schafer R, Spevak W, Weyer U, Wiche-Castanon M, Czernilofsky AP. (1995) Functional characterization of the human neurokinin receptors NK1, NK2, and NK3 based on a cellular assay system. J Recept Signal Transduct Res, 15 (1-4): 617-30. [PMID:8903968]

124. Sundelin JB, Provvedini DM, Wahlestedt CR, Laurell H, Pohl JS, Peterson PA. (1992) Molecular cloning of the murine substance K and substance P receptor genes. Eur J Biochem, 203: 625-631. [PMID:1370937]

125. Takeda Y, Chou KB, Takeda J, Sachais BS, Krause JE. (1991) Molecular cloning, structural characterization and functional expression of the human substance P receptor. Biochem Biophys Res Commun, 179 (3): 1232-40. [PMID:1718267]

126. Tanabe T, Otani H, Bao L, Mikami Y, Yasukura T, Ninomiya T, Ogawa R, Inagaki C. (1996) Intracellular signaling pathway of substance P-induced superoxide production in human neutrophils. Eur J Pharmacol, 299 (1-3): 187-95. [PMID:8901022]

127. Tian Y, Wu LH, Oxender DL, Chung FZ. (1996) The unpredicted high affinities of a large number of naturally occurring tachykinins for chimeric NK1/NK3 receptors suggest a role for an inhibitory domain in determining receptor specificity. J Biol Chem, 271 (34): 20250-7. [PMID:8702757]

128. Tooney PA, Au GG, Chahl LA. (2000) Localisation of tachykinin NK1 and NK3 receptors in the human prefrontal and visual cortex. Neurosci Lett, 283 (3): 185-8. [PMID:10754218]

129. Tooney PA, Au GG, Chahl LA. (2000) Tachykinin NK1 and NK3 receptors in the prefrontal cortex of the human brain. Clin Exp Pharmacol Physiol, 27 (11): 947-9. [PMID:11071316]

130. Torrens Y, Saffroy M, Glowinski J, Beaujouan JC. (1997) Substance P(6-11) and natural tachykinins interact with septide-sensitive tachykinin receptors coupled to a phospholipase C in the rat urinary bladder. Neuropeptides, 31 (3): 243-51. [PMID:9243521]

131. Tousignant C, Guillemette G, Drapeau G, Télémaque S, Dion S, Regoli D. (1990) 125I-BH[Sar9, Met(O2)11]-SP, a new selective ligand for the NK-1 receptor in the central nervous system. Brain Res, 524 (2): 263-70. [PMID:1705465]

132. Tousignant C, Guillemette G, Regoli D. (1991) Binding sites for [3H][Sar9, Met(O2)11]substance P in rat brain and guinea pig ileum. Brain Res, 560 (1-2): 1-11. [PMID:1722129]

133. Tremblay L, Kemel ML, Desban M, Gauchy C, Glowinski J. (1992) Distinct presynaptic control of dopamine release in striosomal- and matrix-enriched areas of the rat striatum by selective agonists of NK1, NK2, and NK3 tachykinin receptors. Proc Natl Acad Sci USA, 89 (23): 11214-8. [PMID:1280822]

134. Trist DG, Ratti E, Bye A. (2013) Why receptor reserve matters for neurokinin1 (NK1) receptor antagonists. J Recept Signal Transduct Res, 33 (6): 333-7. [PMID:24106886]

135. Tsuchiya M, Fujiwara Y, Kanai Y, Mizutani M, Shimada K, Suga O, Ueda S, Watson JW, Nagahisa A. (2002) Anti-emetic activity of the novel nonpeptide tachykinin NK1 receptor antagonist ezlopitant (CJ-11,974) against acute and delayed cisplatin-induced emesis in the ferret. Pharmacology, 66 (3): 144-52. [PMID:12372904]

136. Tumati S, Largent-Milnes TM, Keresztes AI, Yamamoto T, Vanderah TW, Roeske WR, Hruby VJ, Varga EV. (2012) Tachykinin NK₁ receptor antagonist co-administration attenuates opioid withdrawal-mediated spinal microglia and astrocyte activation. Eur J Pharmacol, 684 (1-3): 64-70. [PMID:22724132]

137. Unger T, Carolus S, Demmert G, Ganten D, Lang RE, Maser-Gluth C, Steinberg H, Veelken R. (1988) Substance P induces a cardiovascular defense reaction in the rat: pharmacological characterization. Circ Res, 63: 812-820. [PMID:2458861]

138. Vannucchi MG, Faussone-Pellegrini MS. (2000) NK1, NK2 and NK3 tachykinin receptor localization and tachykinin distribution in the ileum of the mouse. Anat Embryol, 202 (3): 247-55. [PMID:10994997]

139. Wang Y, Wang DH. (2012) Role of substance P in renal injury during DOCA-salt hypertension. Endocrinology, 153 (12): 5972-9. [PMID:23024265]

140. Watanabe Y, Asai H, Ishii T, Kiuchi S, Okamoto M, Taniguchi H, Nagasaki M, Saito A. (2008) Pharmacological characterization of T-2328, 2-fluoro-4'-methoxy-3'-[[[(2S,3S)-2-phenyl-3-piperidinyl]amino]methyl]-[1,1'-biphenyl]-4-carbonitrile dihydrochloride, as a brain-penetrating antagonist of tachykinin NK1 receptor. J Pharmacol Sci, 106 (1): 121-7. [PMID:18187929]

141. Williams R, Zou X, Hoyle GW. (2007) Tachykinin-1 receptor stimulates proinflammatory gene expression in lung epithelial cells through activation of NF-kappaB via a G(q)-dependent pathway. Am J Physiol Lung Cell Mol Physiol, 292 (2): L430-7. [PMID:17041011]

142. Yachnis AT, Crawley JN, Jensen RT, McGrane MM, Moody TW. (1984) The antagonism of bombesin in the CNS by substance P analogues. Life Sci, 35 (19): 1963-9. [PMID:6208451]

143. Yin J, Chapman K, Clark LD, Shao Z, Borek D, Xu Q, Wang J, Rosenbaum DM. (2018) Crystal structure of the human NK1 tachykinin receptor. Proc Natl Acad Sci USA, 115 (52): 13264-13269. [PMID:30538204]

144. Yoshida A, Mobarakeh JI, Sakurai E, Sakurada S, Orito T, Kuramasu A, Kato M, Yanai K. (2005) Intrathecally-administered histamine facilitates nociception through tachykinin NK1 and histamine H1 receptors: a study in histidine decarboxylase gene knockout mice. Eur J Pharmacol, 522 (1-3): 55-62. [PMID:16212954]

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