CaS receptor | Calcium-sensing receptor | IUPHAR Guide to IMMUNOPHARMACOLOGY

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CaS receptor

Target not currently curated in GtoImmuPdb

Target id: 54

Nomenclature: CaS receptor

Family: Calcium-sensing receptor

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

Gene and Protein Information
class C G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 1078 3q21-q24 CASR calcium sensing receptor 75
Mouse 7 1079 16 B3 Casr calcium-sensing receptor 53
Rat 7 1079 11q22 Casr calcium-sensing receptor 94
Previous and Unofficial Names
CaR | GPRC2A | extracellular calcium-sensing receptor | divalent cation-sensing receptor | calcium-sensing receptor
Database Links
Specialist databases
GPCRDB casr_human (Hs), casr_mouse (Mm), casr_rat (Rn)
Other databases
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Orphanet
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia
Natural/Endogenous Ligands
Ca2+
L-tryptophan
Mg2+
spermine
Amino-acid rank order of potency
L-phenylalanine, L-tryptophan, L-histidine > L-alanine > L-serine, L-proline, L-glutamic acid > L-aspartic acid (not L-lysine, L-arginine, L-leucine and L-isoleucine)  [30]
Cation rank order of potency
Gd3+ > Ca2+ > Mg2+  [14]
Glutamyl peptide rank order of potency
S-methylglutathione ≈ γGlu-Val-Gly > glutathione > γGlu-Cys  [10,84,113]
Polyamine rank order of potency
spermine > spermidine > putrescine  [91]

Download all structure-activity data for this target as a CSV file

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
neomycin Rn Full agonist 4.0 pKd 94
pKd 4.0 [94]
spermine Hs Full agonist 3.5 pKd 91
pKd 3.5 [91]
Ca2+ Mm Full agonist 2.5 pKd 89
pKd 2.5 [89]
Ca2+ Rn Full agonist 2.5 pKd 94
pKd 2.5 [94]
Ca2+ Hs Full agonist 2.4 pKd 75
pKd 2.4 [75]
Mg2+ Rn Partial agonist 2.4 pKd 12,94
pKd 2.4 [12,94]
etelcalcetide Hs Agonist 4.6 pEC50 112
pEC50 4.6 (EC50 2.5x10-5 M) [112]
Description: Measuring ligand induced IP1 accumulation.
evocalcet Hs Agonist - - 73
[73]
View species-specific agonist tables
Agonist Comments
Etelcalcetide is a novel peptide agonist of the receptor [112]. Other aminoglycosides show agonist activity [94].

Bovine data is available on a number of other ligands including: polyarginine (and other polycations) (pKd 7) ([15]), Gd3+ and other lanthanides (pKd 4.3-4.9) ([13-14]), neomycin (and other aminoglycosides) (pKd 6.9).
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
2-methyl-3-phenethyl-3H-pyrimidin-4-one Hs Antagonist 7.0 pIC50 105
pIC50 7.0 [105]
compound (S)-3h [PMID: 15686947] Hs Antagonist 6.9 pIC50 122
pIC50 6.9 [122]
compound 17 [PMID: 15300839] Rn Antagonist 5.3 pIC50 55
pIC50 5.3 [55]
1-arylmethylpyrrolidin-2-yl ethanol amine Rn Antagonist 4.3 pIC50 43
pIC50 4.3 [43]
View species-specific antagonist tables
Antagonist Comments
There have been few, if any, studies evaluating whether these are competitive or noncompetitive antagonists. The binding site for polycationic (type 1) CaR agonists, such as calcium or gadolinium, are almost certainly in a different location from that of these antagonists, with the former being predominantly in the amino-terminal extracellular domain and the latter in the transmembrane domains. However, the binding site for the calcimimetic (type 2) CaR activators, at a minimum, overlaps with that of the antagonists [16,48].
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
NPS 2143 Hs Negative 6.2 – 6.7 pKB 33,63-64
pKB 6.2 – 6.7 [33,63-64]
Description: Ca2+i release
tecalcet Hs Positive 6.2 – 6.6 pKB 31,33
pKB 6.2 – 6.6 [31,33]
Description: Ca2+i release
AC265347 Hs Positive 6.3 – 6.4 pKB 31,63
pKB 6.3 – 6.4 [31,63]
Description: Ca2+i release
calindol Hs Positive 6.3 pKB 31
pKB 6.3 [31]
Description: Ca2+i release
cinacalcet Hs Positive 5.9 – 6.6 pKB 31,33,63-64
pKB 5.9 – 6.6 [31,33,63-64]
Description: Ca2+i release
tecalcet Hs Positive 6.5 pKd 80
pKd 6.5 [80]
calindol Hs Positive 6.0 – 6.5 pKd 54,87
pKd 6.0 – 6.5 [54,87]
L-tryptophan Hs Positive 2.6 – 4.4 pKd 29-30
pKd 2.6 – 4.4 [29-30]
AC265347 Hs Positive 7.6 – 8.1 pEC50 66
pEC50 7.6 – 8.1 [66]
cinacalcet Hs Positive 7.3 pEC50 78
pEC50 7.3 (EC50 5.1x10-8 M) [78]
ATF 936 Hs Negative 8.9 pIC50 116
pIC50 8.9 [116]
Description: Inhibition of 2.5 mM Ca2+-mediated Ca2+i release
encaleret Hs Negative 7.9 pIC50 107
pIC50 7.9 [107]
Description: Inhibition of 5 mM Ca2+-mediated luciferase reporter activity
NPS 2143 Hs Negative 7.1 – 7.4 pIC50 77,122
pIC50 7.1 – 7.4 [77,122]
SB-423562 Hs Negative 7.1 pIC50 60
pIC50 7.1 [60]
ronacaleret Hs Negative 6.5 – 6.8 pIC50 5
pIC50 6.5 – 6.8 [5]
calhex 231 Hs Negative 6.4 pIC50 88
pIC50 6.4 [88]
Description: Inhibition of 9mM Ca2+o-mediated IP accumulation
Allosteric Modulator Comments
Note that aromatic amino acids and calcimimetics are ineffective in the absence of Ca2+. N1-Arylsulfonyl-N2-(1-aryl)ethyl-3-phenylpropane-1,2-diamines [32] and cinacalcet [76,104] are also allosteric regulators, but do not have associated affinity values. Activity is also shown by other aromatic amino acids e.g. L-Phe, L-Tyr, L-His. NPS 89636 and AXT-914 have been shown to be negative allosteric modulators of this receptor, although affinity data and a chemical structures are unavailable [36,65].

Additional functional readouts of receptor activity:

tecalcet: functional pKB 5.6 - 6.2 for ERK1/2 phosphorylation (pERK1/2) [31,33], functional pKB 6.8 for inositol phosphate (IP) accumulation [31], functional pKB 9.4 for membrane ruffling [33], pEC50 6.3 for potentiation of 0.5 mM Ca2+-mediated Ca2+i release [80], pEC50 6.5 for potentiation of 2 mM Ca2+-mediated inositol phosphate (IP) accumulation [87].

calindol: functional pKB 5.2 for pERK1/2 [31], functional pKB 6.4 for IP accumulation [31], pEC50 6.5 for potentiation of 2 mM Ca2+-mediated IP accumulation [87].

AC265347: functional pKB 6.3 - 6.7 for pERK1/2 [31,63], functional pKB 8.0 for IP accumulation [31], pEC50 7.6 for potentiation of 1.6 mM Ca2+-mediated cellular proliferation, and pEC50 8.1 for potentiation of 1.6 mM Ca2+-mediated IP accumulation [66].

cinacalcet: functional pKB 5.9 - 6.7 for pERK1/2 [31,33,63-64], functional pKB 6.1 for IP accumulation [31], functional pKB 8.1 for membrane ruffling [33], pEC50 7.3 for potentiation of 0.5 mM Ca2+-mediated Ca2+i release [78].

NPS 2143: functional pKB 6.2 - 6.7 for pERK1/2 [33,63-64], functional pKB 7.8 for membrane ruffling [33], pIC50 7.4 for inhibition of 1.75mM Ca2+-mediated Ca2+i release [77].
Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family
Gq/G11 family
G12/G13 family
Adenylate cyclase inhibition
Phospholipase C stimulation
Phospholipase D stimulation
Comments:  In [51], activation of PLD by the CaR takes place through a direct mechanism involving G12/G13. In some cases, inhibition of adenylate cyclase appears to be indirect, occurring by a calcium sensing receptor-mediated increase in the cytosolic calcium concentration, which then inhibits a calcium-sensitive isoform of adenylate cyclase, see below [34].
References:  18,26,51,56,79
Secondary Transduction Mechanisms
Transducer Effector/Response
Gq/G11 family
G protein (identity unknown)
Adenylate cyclase stimulation
Potassium channel
Phospholipase A2 stimulation
Phospholipase D stimulation
Other - See Comments
Comments:  In addition to the transducers and effectors noted above, the calcium sensing receptor also activates a nonselective cation channel [125], MAPK pathways, e.g. ERK1/2 [46,57,71], p38 MAPK [67], JNK [22], PI-3K [108], PI-4K [50], Rho [90] and the epidermal growth factor receptor [68].
References:  24,34,46,56-57,71,124-125
Tissue Distribution
Pancreatic islet and insulinoma cells
Species:  Human
Technique:  immunocytochemistry.
References:  58
Pancreatic acinar and duct cells.
Pancreatic cancer cells, Capan-1.
Species:  Human
Technique:  RT-PCR and immunocytochemistry.
References:  99
Breast ductal cells.
Species:  Human
Technique:  Northern blotting, RT-PCR and immunocytochemistry.
References:  27
Gastrinoma cells.
Species:  Human
Technique:  Northern blotting, RT-PCR, immunocytochemistry and Western blotting.
References:  52
C-cells.
Species:  Human
Technique:  in situ hybridization.
References:  40
Breast cancer cell lines, MCF-7 and MDA-MB-231.
Species:  Human
Technique:  Northern blotting, RT-PCR, immunocytochemistry and Western blotting.
References:  102
Osteosarcoma cell line, MG-63.
Species:  Human
Technique:  Northern blotting, RT-PCR, immunocytochemistry and Western blotting.
References:  119
Osteoblastic cells, SaOS-2.
Species:  Human
Technique:  Western blotting.
References:  19
Lens epithelial cells.
Species:  Human
Technique:  Northern blotting, RT-PCR and immunocytochemistry.
References:  25
Colon cancer cells, Caco-2.
Species:  Human
Technique:  RT-PCR, immunocytochemistry and Western blotting.
References:  62
Minor salivary gland.
Species:  Human
Technique:  Northern blotting.
References:  47
Prostate cancer cells, PC-3 and LnCaP.
Species:  Human
Technique:  Northern blotting, RT-PCR, immunocytochemistry and Western blotting.
References:  123
Ovarian surface cells.
Species:  Human
Technique:  Northern and Western blotting.
References:  70
Promyelocytic leukemia cells, HL-60.
Species:  Human
Technique:  Northern blotting, RT-PCR, immunocytochemistry and Western blotting.
References:  121
Myeloma cells, U266, IM-9 and RPM18226.
Species:  Human
Technique:  RT-PCR, immunocytochemistry and Western blotting.
References:  120
Medullary thyroid cancer, normal and adenomatous parathyroid, normal and adenomatous pituitary.
Species:  Human
Technique:  RT-PCR.
References:  69
Keratinocytes.
Species:  Human
Technique:  Northern blotting, RT-PCR, immunocytochemistry and Western blotting.
References:  38
Pituitary.
Species:  Human
Technique:  Northern blotting.
References:  69
Monocytes.
Species:  Human
Technique:  Northern blotting.
References:  85
Embryonic astrocytes, astrocytomas and meningiomas.
Species:  Human
Technique:  Northern blotting, RT-PCR and Western blotting.
References:  21
Gastric mucosal epithelial cells.
Species:  Human
Technique:  Immunocytochemistry and Western blotting.
References:  98
Parathyroid.
Species:  Human
Technique:  Northern blotting.
References:  75
Thyroid c-cells.
Species:  Human
Technique:  RT-PCR.
References:  42
Placental villi (cytotrophoblasts and synctiotrophoblasts), trophoblast columns.
Species:  Human
Technique:  Northern blotting, RT-PCR, in situ hybridisation and immunocytochemistry.
References:  8
Colon.
Species:  Human
Technique:  RT-PCR, immunocytochemistry and Western blotting.
References:  106
Pancreatic islet and insulinoma cells.
Species:  Human
Technique:  RT-PCR.
References:  52,99
Osteoblastic cell line, MC3T3-E1.
Species:  Mouse
Technique:  Northern blotting, RT-PCR, immunocytochemistry and Western blotting.
References:  118
Pituitary cell line, AtT-20.
Species:  Mouse
Technique:  Northern blotting, RT-PCR and immunocytochemistry.
References:  37
Skin.
Species:  Mouse
Technique:  RT-PCR and immunocytochemistry.
References:  59
Mesangial cells.
Species:  Mouse
Technique:  RT-PCR, immunocytochemistry and Western blotting.
References:  61
Monocytic cell line, J774.
Species:  Mouse
Technique:  Northern blotting, RT-PCR, immunocytochemistry and Western blotting.
References:  37
Kidney.
Species:  Mouse
Technique:  Immunocytochemistry and Western blotting.
References:  49
Breast.
Species:  Mouse
Technique:  RNAse protection and immunocytochemistry.
References:  110
Parathyroid.
Species:  Mouse
Technique:  immunocytochemistry.
References:  49
Bone marrow stromal cell line, ST-2.
Species:  Mouse
Technique:  Northern blotting, RT-PCR, immunocytochemistry and Western blotting.
References:  117
Osteoblasts, osteoclasts, osteocytes and chondrocytes.
Species:  Mouse
Technique:  In situ hybridisation and immunocytochemistry.
References:  19
Osteoblast, osteocyte and osteoclast.
Species:  Rat
Technique:  immunocytochemistry.
References:  36
Kidney.
Species:  Rat
Technique:  Northern blot and RT-PCR.
References:  93,95
Fibroblasts.
Species:  Rat
Technique:  Northern and Western blotting.
References:  71
Osteoblasts, osteoclasts and osteocytes.
Species:  Rat
Technique:  RT-PCR.
References:  36
Osteoblasts, osteoclasts, osteocytes and chondrocytes.
Species:  Rat
Technique:  immunocytochemistry.
References:  19
Oligodendrocytes.
Species:  Rat
Technique:  RT-PCR, immunocytochemistry and Western blotting.
References:  25
Pancreas, adrenal medulla, testis, multiple brain regions.
Species:  Rat
Technique:  immunocytochemistry.
References:  72
Small and large intestine.
Species:  Rat
Technique:  immunocytochemistry.
References:  20,72
Kidney.
Species:  Rat
Technique:  immunocytochemistry.
References:  72,95
Kidney inner medullary collecting duct.
Species:  Rat
Technique:  Western blotting.
References:  103
Kidney proximal tubule.
Species:  Rat
Technique:  immunocytochemistry.
References:  95
Stomach.
Species:  Rat
Technique:  immunocytochemistry.
References:  28,72
Parathyroid and kidney.
Species:  Rat
Technique:  Ribonuclease protection assay.
References:  11
Liver.
Species:  Rat
Technique:  Immunocytochemistry and Western blotting.
References:  17
Heart.
Species:  Rat
Technique:  Western blotting.
References:  72
C-cells.
Species:  Rat
Technique:  immunocytochemistry.
References:  40
Thyroid c-cells.
Species:  Rat
Technique:  Northern blotting, in situ hybridisation and immunocytochemistry.
References:  42
Microglia.
Species:  Rat
Technique:  Northern blotting, RT-PCR, immunocytochemistry and Western blotting.
References:  24
Sensory nerve.
Species:  Rat
Technique:  Western blotting.
References:  115
Testicular cancer cell-line H-500.
Species:  Rat
Technique:  RT-PCR, Western blot, immunocytochemistry.
References:  100
Fibroblasts.
Species:  Rat
Technique:  Northern blot.
References:  71
C-cells.
Species:  Rat
Technique:  Northern blot.
References:  40,42
Stomach.
Species:  Rat
Technique:  Northern blot.
References:  28
Small and large intestine.
Species:  Rat
Technique:  Northern blot.
References:  20
Oligodendrocytes.
Species:  Rat
Technique:  Northern blot and RT-PCR.
References:  23
Oligodendrocytes.
Species:  Rat
Technique:  Northern blot and RT-PCR.
References:  23
Microglia.
Species:  Rat
Technique:  Northern blot, RT-PCR and immunocytochemistry.
References:  24
Testicular cancer cell (H-500).
Species:  Rat
Technique:  Northern blot and RT-PCR.
References:  100
Medullary thyroid cancer cell line (rMTC44-2).
Species:  Rat
Technique:  RT-PCR.
References:  42
Heart.
Species:  Rat
Technique:  RT-PCR.
References:  114
Osteoblast, osteocyte and osteoclast.
Species:  Rat
Technique:  RT-PCR.
References:  36
Multiple brain regions.
Species:  Rat
Technique:  in situ hybridization.
References:  97
Osteoblast, osteocyte, osteocyte and chondrocyte.
Species:  Rat
Technique:  in situ hybridization.
References:  19
Kidney.
Species:  Rat
Technique:  immunocytochemistry.
References:  72
Tissue Distribution Comments
A variety of techniques--Northern blotting, RT-PCR, immunocytochemistry and Western blotting--were used to identify the calcium sensing receptor in the receptor distribution studies. Lack of availability of some human tissues, such as kidney, have so far precluded a comprehensive tissue survery for expression of the human calcium sensing receptor in humans.
Expression Datasets

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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
Effects of agonists/allosteric regulators on human calcium sensing receptor-transfected HEK 293 cells.
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  Increase in cytosolic calcium concentration, inhibition of adenylate cyclase, stimulation of inositol phosphate generation, activation of MAPK.
References:  4,18,57
Effects of agonists/allosteric regulators on rat calcium sensing receptor-transfected CHO cells.
Species:  Rat
Tissue:  CHO cells.
Response measured:  Stimulation of inositol phosphate generation, inhibition of adenylate cyclase.
References:  55,88
Measurement of cytosolic calcium concentration, adenylate cyclase activity, inositol phosphate generatation and activity of MAPK.
Species:  Mouse
Tissue:  AtT-20 cells.
Response measured:  Increase in intracellular Ca2+, inhibition of adenylate cyclase, stimulation of inositol phosphate generation, activation of MAPK.
References:  37
Functional Assay Comments
In addition to these two calcium sensing receptor transfected cell systems, measurement of the same responses AtT-20 cells [55] have also proven to be useful test systems.
Physiological Functions
Inhibition of PTH secretion and parathyroid cellular proliferation.
Species:  Human
Tissue:  Parathyroid glands or cells.
References:  76,80
Inhibition of PTH secretion and parathyroid cellular proliferation.
Species:  Rat
Tissue:  Parathyroid glands or cells.
References:  111
Inhibition of PTH-stimulated phosphate excretion in the proximal tubule.
Species:  Mouse
Tissue:  Microdissected in vitro tubule preparations.
References:  3
Inhibition of vasopressin-stimulated reabsorption of water in the renal inner medullary collecting duct.
Species:  Rat
Tissue:  Microdissected in vitro tubule preparations.
References:  103
Stimulation of PTHrP secretion in vitro.
Species:  Human
Tissue:  Prostate cell line.
References:  101
Stimulation of calcitonin secretion from thyroidal C-cells.
Species:  Rat
Tissue:  C-cell cell line rMTC44-2.
References:  42
Stimulation of calcitonin secretion from thyroidal C-cells.
Species:  Human
Tissue:  C-cell cell lines.
References:  40
Promotion of differentiation of keratinocytes.
Species:  Mouse
Tissue:  Primary cultures of keratinocytes, intact mouse epidermis in vivo.
References:  59,81,109
Stimulation of secretion of ACTH.
Species:  Mouse
Tissue:  Studies using the murine AtT-20 cell line.
References:  39
Stimulation of secretion of ACTH.
Species:  Human
Tissue:  In vivo.
References:  45
Inhibition of PTH secretion and parathyroid cellular proliferation.
Species:  Mouse
Tissue:  Parathyroid glands or cells.
References:  49
Inhibition of renal tubular reabsorption of calcium and magnesium in the renal thick ascending limb.
Species:  Mouse
Tissue:  Microdissected in vitro tubule preparations.
References:  7,35,74
Stimulation of PTHrP secretion in vitro.
Species:  Human
Tissue:  Breast and prostate cancer cell lines.
References:  101-102
Stimulation of PTHrP secretion in vitro.
Species:  Rat
Tissue:  Testicular cancer cells line H-500.
References:  100
Stimulation of calcitonin secretion from thyroidal C-cells.
Species:  Mouse
Tissue:  In vivo.
References:  41
Inhibition of PTHrP secretion in vitro and in vivo.
Species:  Mouse
Tissue:  Breast epithelial cells.
References:  110
Regulation of hematopoietic cell retention in bone marrow.
Species:  Mouse
Tissue:  Hematopoietic stem cells.
References:  1
Inhibition of colonic fluid secretion.
Species:  Rat
Tissue:  Perfused colon crypts.
References:  44
Stimulation of expression of cyclooxygenase COX-2.
Species:  Human
Tissue:  Jaw cyst fibroblasts.
References:  83
Regulation of secretion of BMP-2 and Noggin.
Species:  Human
Tissue:  18Co colonic myofibroblasts.
References:  86
Regulation in intracellular pH.
Species:  Mouse
Tissue:  In vitro perfused cells of the medullary thick ascending limb.
References:  2
Regulation of expression/secretion of chemokines (CXCL-9, CXCL-10 and MCP-3).
Species:  Mouse
Tissue:  GnRH neurons.
References:  6
Stimulation of gastric acid secretion.
Species:  Mouse
Tissue:  Gastric glands in vitro.
References:  92
Inhibition of proliferation of colonic crypt cells.
Species:  Human
Tissue:  Colon cancer cell line.
References:  62
Stimulation of non-selective cation channel.
Species:  Rat
Tissue:  Hippocampal neurons.
References:  125
Modulation of chondrocyte differentiation.
Species:  Mouse
Tissue:  Cultured chondrocyte cells.
References:  96
Physiological Consequences of Altering Gene Expression
Absent expression of calcium-sensing receptor in calcium receptor knockout mice removes the tonic inhibitory action of extracellular calcium on PTH secretion and parathyroid cellular proliferation and impairs keratinocyte differentiation.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  49,59,81
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Casrtm1Ces Casrtm1Ces/Casrtm1Ces
involves: 129X1/SvJ * Black Swiss
MGI:1351351  MP:0002896 abnormal bone mineralization PMID: 11517179 
Casrtm1Ces Casrtm1Ces/Casrtm1Ces
involves: 129X1/SvJ * Black Swiss
MGI:1351351  MP:0000678 abnormal parathyroid gland morphology PMID: 7493018 
Casrtm1Ces Casrtm1Ces/Casrtm1Ces
involves: 129X1/SvJ * Black Swiss
MGI:1351351  MP:0002980 abnormal postural reflex PMID: 7493018 
Casrtm1Ces Casrtm1Ces/Casrtm1Ces
involves: 129X1/SvJ * Black Swiss
MGI:1351351  MP:0001504 abnormal posture PMID: 7493018 
Casrtm1Ces Casrtm1Ces/Casrtm1Ces
involves: 129X1/SvJ * Black Swiss
MGI:1351351  MP:0001438 aphagia PMID: 7493018 
CasrNuf CasrNuf/CasrNuf
involves: 102/Ei * C3H/He
MGI:1351351  MP:0003195 calcinosis PMID: 15347804 
CasrNuf CasrNuf/CasrNuf
involves: 102/Ei * C3H/He
MGI:1351351  MP:0001304 cataracts PMID: 15347804 
Casr+|CasrNuf CasrNuf/Casr+
either: (involves: 102/Ei * 102/H * C3H/He) or (involves: 102/Ei * C3H/He * C3H/HeH)
MGI:1351351  MP:0001304 cataracts PMID: 15347804 
Casrtm1Ces Casrtm1Ces/Casrtm1Ces
involves: 129X1/SvJ * Black Swiss
MGI:1351351  MP:0001265 decreased body size PMID: 11517179 
Casrtm1Ces Casrtm1Ces/Casrtm1Ces
involves: 129X1/SvJ * Black Swiss
MGI:1351351  MP:0001262 decreased body weight PMID: 11517179 
Casrtm1Ces Casrtm1Ces/Casrtm1Ces
involves: 129X1/SvJ * Black Swiss
MGI:1351351  MP:0000063 decreased bone density PMID: 7493018 
CasrNuf CasrNuf/CasrNuf
involves: 102/Ei * C3H/He
MGI:1351351  MP:0002905 decreased circulating parathyroid hormone level PMID: 15347804 
Casr+|CasrNuf CasrNuf/Casr+
either: (involves: 102/Ei * 102/H * C3H/He) or (involves: 102/Ei * C3H/He * C3H/HeH)
MGI:1351351  MP:0002905 decreased circulating parathyroid hormone level PMID: 15347804 
Casrtm1Ces Casrtm1Ces/Casrtm1Ces
involves: 129X1/SvJ * Black Swiss
MGI:1351351  MP:0001429 dehydration PMID: 7493018 
Casrtm1Ces Casrtm1Ces/Casrtm1Ces
involves: 129X1/SvJ * Black Swiss
MGI:1351351  MP:0000060 delayed bone ossification PMID: 11517179 
Casrtm1Ces Casrtm1Ces/Casrtm1Ces
involves: 129X1/SvJ * Black Swiss
MGI:1351351  MP:0003112 enlarged parathyroid gland PMID: 7493018 
Casrtm1Ces Casrtm1Ces/Casrtm1Ces
involves: 129X1/SvJ * Black Swiss
MGI:1351351  MP:0000194 hypercalcemia PMID: 7493018 
Casr+|Casrtm1Ces Casrtm1Ces/Casr+
involves: 129X1/SvJ * Black Swiss
MGI:1351351  MP:0000194 hypercalcemia PMID: 7493018 
CasrNuf CasrNuf/CasrNuf
involves: 102/Ei * C3H/He
MGI:1351351  MP:0001566 hyperphosphatemia PMID: 15347804 
Casr+|CasrNuf CasrNuf/Casr+
either: (involves: 102/Ei * 102/H * C3H/He) or (involves: 102/Ei * C3H/He * C3H/HeH)
MGI:1351351  MP:0001566 hyperphosphatemia PMID: 15347804 
CasrNuf CasrNuf/CasrNuf
involves: 102/Ei * C3H/He
MGI:1351351  MP:0000195 hypocalcemia PMID: 15347804 
Casr+|CasrNuf CasrNuf/Casr+
either: (involves: 102/Ei * 102/H * C3H/He) or (involves: 102/Ei * C3H/He * C3H/HeH)
MGI:1351351  MP:0000195 hypocalcemia PMID: 15347804 
Casrtm1Ces Casrtm1Ces/Casrtm1Ces
involves: 129X1/SvJ * Black Swiss
MGI:1351351  MP:0002986 hypocalciuria PMID: 7493018 
Casr+|Casrtm1Ces Casrtm1Ces/Casr+
involves: 129X1/SvJ * Black Swiss
MGI:1351351  MP:0002986 hypocalciuria PMID: 7493018 
CasrNuf CasrNuf/CasrNuf
involves: 102/Ei * C3H/He
MGI:1351351  MP:0002986 hypocalciuria PMID: 15347804 
Casrtm1Ces Casrtm1Ces/Casrtm1Ces
involves: 129X1/SvJ * Black Swiss
MGI:1351351  MP:0000198 hypophosphatemia PMID: 11517179 
CasrNuf CasrNuf/CasrNuf
involves: 102/Ei * C3H/He
MGI:1351351  MP:0002902 hypophosphaturia PMID: 15347804 
Casrtm1Ces Casrtm1Ces/Casrtm1Ces
involves: 129X1/SvJ * Black Swiss
MGI:1351351  MP:0010092 increased circulating magnesium level PMID: 7493018 
Casr+|Casrtm1Ces Casrtm1Ces/Casr+
involves: 129X1/SvJ * Black Swiss
MGI:1351351  MP:0010092 increased circulating magnesium level PMID: 7493018 
Casrtm1Ces Casrtm1Ces/Casrtm1Ces
involves: 129X1/SvJ * Black Swiss
MGI:1351351  MP:0002904 increased circulating parathyroid hormone level PMID: 7493018 
Casr+|Casrtm1Ces Casrtm1Ces/Casr+
involves: 129X1/SvJ * Black Swiss
MGI:1351351  MP:0002904 increased circulating parathyroid hormone level PMID: 7493018 
Casrtm1Ces Casrtm1Ces/Casrtm1Ces
involves: 129X1/SvJ * Black Swiss
MGI:1351351  MP:0002608 increased hematocrit PMID: 7493018 
CasrNuf CasrNuf/CasrNuf
involves: 102/Ei * C3H/He
MGI:1351351  MP:0001846 increased inflammatory response PMID: 15347804 
Casrtm1Ces Casrtm1Ces/Casrtm1Ces
involves: 129X1/SvJ * Black Swiss
MGI:1351351  MP:0003408 increased width of hypertrophic chondrocyte zone PMID: 11517179 
Casrtm1Ces Casrtm1Ces/Casrtm1Ces
involves: 129X1/SvJ * Black Swiss
MGI:1351351  MP:0000069 kyphoscoliosis PMID: 7493018 
Casrtm1Ces Casrtm1Ces/Casrtm1Ces
involves: 129X1/SvJ * Black Swiss
MGI:1351351  MP:0005202 lethargy PMID: 7493018 
CasrNuf CasrNuf/CasrNuf
involves: 102/Ei * C3H/He
MGI:1351351  MP:0003199 muscle calcification PMID: 15347804 
Casrtm1Ces Casrtm1Ces/Casrtm1Ces
involves: 129X1/SvJ * Black Swiss
MGI:1351351  MP:0003114 pigmented parathyroid gland PMID: 7493018 
Casrtm1Ces Casrtm1Ces/Casrtm1Ces
involves: 129X1/SvJ * Black Swiss
MGI:1351351  MP:0001732 postnatal growth retardation PMID: 7493018 
Casrtm1Ces Casrtm1Ces/Casrtm1Ces
involves: 129X1/SvJ * Black Swiss
MGI:1351351  MP:0002082 postnatal lethality PMID: 11517179  7493018 
CasrNuf CasrNuf/CasrNuf
involves: 102/Ei * C3H/He
MGI:1351351  MP:0002083 premature death PMID: 15347804 
Casrtm1Ces Casrtm1Ces/Casrtm1Ces
involves: 129X1/SvJ * Black Swiss
MGI:1351351  MP:0003116 rickets PMID: 11517179 
Clinically-Relevant Mutations and Pathophysiology
Disease:  Epilepsy, idiopathic generalized, susceptibility to, 8; EIG8
Synonyms: Idiopathic generalized epilepsy [Disease Ontology: DOID:1827]
Disease Ontology: DOID:1827
OMIM: 612899
Disease:  Familial hypocalciuric hypercalcemia type 1
OMIM: 145980
Orphanet: ORPHA93372
Disease:  Familial isolated hypoparathyroidism due to impaired PTH secretion
Orphanet: ORPHA189466
Disease:  Hypocalcemia, autosomal dominant, with Bartter syndrome
Synonyms: Autosomal dominant hypocalcemia [Orphanet: ORPHA428]
Bartter syndrome with hypocalcemia [Orphanet: ORPHA263417]
OMIM: 601198
Orphanet: ORPHA428, ORPHA263417
Disease:  Neonatal severe primary hyperparathyroidism
OMIM: 239200
Orphanet: ORPHA417
Biologically Significant Variants
Type:  Splice variant
Species:  Mouse
Description:  Calcium-sensing receptor expressed in differentiating keratinocytes that lacks exon 5 and has been suggested to exert a dominant negative action on the full length receptor, although some other data suggest that it may harbor some intrinsic biological activity.
References:  59,81-82
Type:  Splice variant
Species:  Human
Description:  Calcium sensing receptor expressed in placental cytotrophoblasts and parathyroid gland that lacks exon 3. Its function is unknown.
References:  9

References

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1. Adams GB, Chabner KT, Alley IR, Olson DP, Szczepiorkowski ZM, Poznansky MC, Kos CH, Pollak MR, Brown EM, Scadden DT. (2006) Stem cell engraftment at the endosteal niche is specified by the calcium-sensing receptor. Nature, 439 (7076): 599-603. [PMID:16382241]

2. Aslanova UF, Morimoto T, Farajov EI, Kumagai N, Nishino M, Sugawara N, Ohsaga A, Maruyama Y, Tsuchiya S, Takahashi S et al.. (2006) Chloride-dependent intracellular pH regulation via extracellular calcium-sensing receptor in the medullary thick ascending limb of the mouse kidney. Tohoku J. Exp. Med., 210 (4): 291-300. [PMID:17146194]

3. Ba J, Brown D, Friedman PA. (2003) Calcium-sensing receptor regulation of PTH-inhibitable proximal tubule phosphate transport. Am. J. Physiol. Renal Physiol., 285 (6): F1233-43. [PMID:12952858]

4. Bai M, Quinn S, Trivedi S, Kifor O, Pearce SH, Pollak MR, Krapcho K, Hebert SC, Brown EM. (1996) Expression and characterization of inactivating and activating mutations in the human Ca2+o-sensing receptor. J. Biol. Chem., 271 (32): 19537-45. [PMID:8702647]

5. Balan G, Bauman J, Bhattacharya S, Castrodad M, Healy DR, Herr M, Humphries P, Jennings S, Kalgutkar AS, Kapinos B et al.. (2009) The discovery of novel calcium sensing receptor negative allosteric modulators. Bioorg. Med. Chem. Lett., 19 (12): 3328-32. [PMID:19442519]

6. Bandyopadhyay S, Jeong KH, Hansen JT, Vassilev PM, Brown EM, Chattopadhyay N. (2007) Calcium-sensing receptor stimulates secretion of an interferon-gamma-induced monokine (CXCL10) and monocyte chemoattractant protein-3 in immortalized GnRH neurons. J. Neurosci. Res., 85 (4): 882-95. [PMID:17285630]

7. Blankenship KA, Williams JJ, Lawrence MS, McLeish KR, Dean WL, Arthur JM. (2001) The calcium-sensing receptor regulates calcium absorption in MDCK cells by inhibition of PMCA. Am. J. Physiol. Renal Physiol., 280 (5): F815-22. [PMID:11292623]

8. Bradbury RA, Cropley J, Kifor O, Lovicu FJ, de Iongh RU, Kable E, Brown EM, Seely EW, Peat BB, Conigrave AD. (2002) Localization of the extracellular Ca(2+)-sensing receptor in the human placenta. Placenta., 23: 192-200. [PMID:11945086]

9. Bradbury RA, Sunn KL, Crossley M, Bai M, Brown EM, Delbridge L, Conigrave AD. (1998) Expression of the parathyroid Ca(2+)-sensing receptor in cytotrophoblasts from human term placenta. J. Endocrinol., 156 (3): 425-30. [PMID:9582498]

10. Broadhead GK, Mun HC, Avlani VA, Jourdon O, Church WB, Christopoulos A, Delbridge L, Conigrave AD. (2011) Allosteric modulation of the calcium-sensing receptor by gamma-glutamyl peptides: inhibition of PTH secretion, suppression of intracellular cAMP levels, and a common mechanism of action with L-amino acids. J. Biol. Chem., 286 (11): 8786-97. [PMID:21187282]

11. Brown AJ, Zhong M, Finch J, Ritter C, McCracken R, Morrissey J, Slatopolsky E. (1996) Rat calcium-sensing receptor is regulated by vitamin D but not by calcium. Am. J. Physiol., 270 (3 Pt 2): F454-60. [PMID:8780248]

12. Brown EM, Chen CJ. (1989) Calcium, magnesium and the control of PTH secretion. Bone Miner, 5 (3): 249-57. [PMID:2655774]

13. Brown EM, Fuleihan G el-H, Chen CJ, Kifor O. (1990) A comparison of the effects of divalent and trivalent cations on parathyroid hormone release, 3',5'-cyclic-adenosine monophosphate accumulation, and the levels of inositol phosphates in bovine parathyroid cells. Endocrinology, 127 (3): 1064-71. [PMID:2167204]

14. Brown EM, Gamba G, Riccardi D, Lombardi M, Butters R, Kifor O, Sun A, Hediger MA, Lytton J, Hebert SC. (1993) Cloning and characterization of an extracellular Ca(2+)-sensing receptor from bovine parathyroid. Nature, 366 (6455): 575-80. [PMID:8255296]

15. Brown EM, Katz C, Butters R, Kifor O. (1991) Polyarginine, polylysine, and protamine mimic the effects of high extracellular calcium concentrations on dispersed bovine parathyroid cells. J. Bone Miner. Res., 6 (11): 1217-25. [PMID:1666808]

16. Bräuner-Osborne H, Jensen AA, Sheppard PO, O'Hara P, Krogsgaard-Larsen P. (1999) The agonist-binding domain of the calcium-sensing receptor is located at the amino-terminal domain. J. Biol. Chem., 274 (26): 18382-6. [PMID:10373443]

17. Canaff L, Petit JL, Kisiel M, Watson PH, Gascon-Barré M, Hendy GN. (2001) Extracellular calcium-sensing receptor is expressed in rat hepatocytes. coupling to intracellular calcium mobilization and stimulation of bile flow. J. Biol. Chem., 276 (6): 4070-9. [PMID:11071898]

18. Chang W, Pratt S, Chen TH, Nemeth E, Huang Z, Shoback D. (1998) Coupling of calcium receptors to inositol phosphate and cyclic AMP generation in mammalian cells and Xenopus laevis oocytes and immunodetection of receptor protein by region-specific antipeptide antisera. J Bone Miner Res., 13: 570-580. [PMID:9556057]

19. Chang W, Tu C, Chen TH, Komuves L, Oda Y, Pratt SA, Miller S, Shoback D. (1999) Expression and signal transduction of calcium-sensing receptors in cartilage and bone. Endocrinology, 140 (12): 5883-93. [PMID:10579354]

20. Chattopadhyay N, Cheng I, Rogers K, Riccardi D, Hall A, Diaz R, Hebert SC, Soybel DI, Brown EM. (1998) Identification and localization of extracellular Ca(2+)-sensing receptor in rat intestine. Am. J. Physiol., 274 (1): G122-30. [PMID:9458781]

21. Chattopadhyay N, Evliyaoglu C, Heese O, Carroll R, Sanders J, Black P, Brown EM. (2000) Regulation of secretion of PTHrP by Ca(2+)-sensing receptor in human astrocytes, astrocytomas, and meningiomas. Am. J. Physiol., Cell Physiol., 279 (3): C691-9. [PMID:10942719]

22. Chattopadhyay N, Yano S, Tfelt-Hansen J, Rooney P, Kanuparthi D, Bandyopadhyay S, Ren X, Terwilliger E, Brown EM. (2004) Mitogenic action of calcium-sensing receptor on rat calvarial osteoblasts. Endocrinology, 145 (7): 3451-62. [PMID:15084499]

23. Chattopadhyay N, Ye C, Singh DP, Kifor O, Vassilev PM, Shinohara T, Chylack Jr LT, Brown EM. (1997) Expression of extracellular calcium-sensing receptor by human lens epithelial cells. Biochem. Biophys. Res. Commun., 233 (3): 801-5. [PMID:9168937]

24. Chattopadhyay N, Ye C, Yamaguchi T, Nakai M, Kifor O, Vassilev PM, Nishimura RN, Brown EM. (1999) The extracellular calcium-sensing receptor is expressed in rat microglia and modulates an outward K+ channel. J. Neurochem., 72 (5): 1915-22. [PMID:10217268]

25. Chattopadhyay N, Ye CP, Yamaguchi T, Kifor O, Vassilev PM, Nishimura R, Brown EM. (1998) Extracellular calcium-sensing receptor in rat oligodendrocytes: expression and potential role in regulation of cellular proliferation and an outward K+ channel. Glia, 24 (4): 449-58. [PMID:9814825]

26. Chen CJ, Barnett JV, Congo DA, Brown EM. (1989) Divalent cations suppress 3',5'-adenosine monophosphate accumulation by stimulating a pertussis toxin-sensitive guanine nucleotide-binding protein in cultured bovine parathyroid cells. Endocrinology, 124 (1): 233-9. [PMID:2462488]

27. Cheng I, Klingensmith ME, Chattopadhyay N, Kifor O, Butters RR, Soybel DI, Brown EM. (1998) Identification and localization of the extracellular calcium-sensing receptor in human breast. J. Clin. Endocrinol. Metab., 83 (2): 703-7. [PMID:9467597]

28. Cheng I, Qureshi I, Chattopadhyay N, Qureshi A, Butters RR, Hall AE, Cima RR, Rogers KV, Hebert SC, Geibel JP et al.. (1999) Expression of an extracellular calcium-sensing receptor in rat stomach. Gastroenterology, 116 (1): 118-26. [PMID:9869609]

29. Conigrave AD, Mun HC, Delbridge L, Quinn SJ, Wilkinson M, Brown EM. (2004) L-amino acids regulate parathyroid hormone secretion. J. Biol. Chem., 279 (37): 38151-9. [PMID:15234970]

30. Conigrave AD, Quinn SJ, Brown EM. (2000) L-amino acid sensing by the extracellular Ca2+-sensing receptor. Proc. Natl. Acad. Sci. U.S.A., 97 (9): 4814-9. [PMID:10781086]

31. Cook AE, Mistry SN, Gregory KJ, Furness SG, Sexton PM, Scammells PJ, Conigrave AD, Christopoulos A, Leach K. (2015) Biased allosteric modulation at the CaS receptor engendered by structurally diverse calcimimetics. Br. J. Pharmacol., 172 (1): 185-200. [PMID:25220431]

32. Dauban P, Ferry S, Faure H, Ruat M, Dodd RH. (2000) N1-Arylsulfonyl-N2-(1-aryl)ethyl-3-phenylpropane-1,2-diamines as novel calcimimetics acting on the calcium sensing receptor. Bioorg. Med. Chem. Lett., 10 (17): 2001-4. [PMID:10987436]

33. Davey AE, Leach K, Valant C, Conigrave AD, Sexton PM, Christopoulos A. (2012) Positive and negative allosteric modulators promote biased signaling at the calcium-sensing receptor. Endocrinology, 153 (3): 1232-41. [PMID:22210744]

34. de Jesus Ferreira MC, Héliès-Toussaint C, Imbert-Teboul M, Bailly C, Verbavatz JM, Bellanger AC, Chabardès D. (1998) Co-expression of a Ca2+-inhibitable adenylyl cyclase and of a Ca2+-sensing receptor in the cortical thick ascending limb cell of the rat kidney. Inhibition of hormone-dependent cAMP accumulation by extracellular Ca2+. J. Biol. Chem., 273 (24): 15192-202. [PMID:9614133]

35. Desfleurs E, Wittner M, Pajaud S, Nitschke R, Rajerison RM, Di Stefano A. (1999) The Ca2+-sensing receptor in the rabbit cortical thick ascending limb (CTAL) is functionally not coupled to phospholipase C. Pflugers Arch., 437 (5): 716-23. [PMID:10087149]

36. Dvorak MM, Siddiqua A, Ward DT, Carter DH, Dallas SL, Nemeth EF, Riccardi D. (2004) Physiological changes in extracellular calcium concentration directly control osteoblast function in the absence of calciotropic hormones. Proc. Natl. Acad. Sci. U.S.A., 101 (14): 5140-5. [PMID:15051872]

37. Emanuel RL, Adler GK, Kifor O, Quinn SJ, Fuller F, Krapcho K, Brown EM. (1996) Calcium-sensing receptor expression and regulation by extracellular calcium in the AtT-20 pituitary cell line. Mol. Endocrinol., 10 (5): 555-65. [PMID:8732686]

38. Fatherazi S, Belton CM, Cai S, Zarif S, Goodwin PC, Lamont RJ, Izutsu KT. (2004) Calcium receptor message, expression and function decrease in differentiating keratinocytes. Pflugers Arch., 448: 93-104. [PMID:14770313]

39. Ferry S, Chatel B, Dodd RH, Lair C, Gully D, Maffrand JP, Ruat M. (1997) Effects of divalent cations and of a calcimimetic on adrenocorticotropic hormone release in pituitary tumor cells. Biochem. Biophys. Res. Commun., 238 (3): 866-73. [PMID:9325183]

40. Freichel M, Zink-Lorenz A, Holloschi A, Hafner M, Flockerzi V, Raue F. (1996) Expression of a calcium-sensing receptor in a human medullary thyroid carcinoma cell line and its contribution to calcitonin secretion. Endocrinology, 137 (9): 3842-8. [PMID:8756555]

41. Fudge NJ, Kovacs CS. (2004) Physiological studies in heterozygous calcium sensing receptor (CaSR) gene-ablated mice confirm that the CaSR regulates calcitonin release in vivo. BMC Physiol., 4: 5. [PMID:15099400]

42. Garrett JE, Tamir H, Kifor O, Simin RT, Rogers KV, Mithal A, Gagel RF, Brown EM. (1995) Calcitonin-secreting cells of the thyroid express an extracellular calcium receptor gene. Endocrinology, 136 (11): 5202-11. [PMID:7588259]

43. Gavai AV, Vaz RJ, Mikkilineni AB, Roberge JY, Liu Y, Lawrence RM, Corte JR, Yang W, Bednarz M, Dickson Jr JK et al.. (2005) Discovery of novel 1-arylmethyl pyrrolidin-2-yl ethanol amines as calcium-sensing receptor antagonists. Bioorg. Med. Chem. Lett., 15 (24): 5478-82. [PMID:16216508]

44. Geibel J, Sritharan K, Geibel R, Geibel P, Persing JS, Seeger A, Roepke TK, Deichstetter M, Prinz C, Cheng SX, Martin D, Hebert SC. (2006) Calcium-sensing receptor abrogates secretagogue- induced increases in intestinal net fluid secretion by enhancing cyclic nucleotide destruction. Proc Natl Acad Sci U S A, 103: 9390-9397. [PMID:16760252]

45. Haden ST, Brown EM, Stoll AL, Scott J, Fuleihan GE. (1999) The effect of lithium on calcium-induced changes in adrenocorticotrophin levels. J. Clin. Endocrinol. Metab., 84 (1): 198-200. [PMID:9920083]

46. Handlogten ME, Huang C, Shiraishi N, Awata H, Miller RT. (2001) The Ca2+-sensing receptor activates cytosolic phospholipase A2 via a Gqalpha -dependent ERK-independent pathway. J. Biol. Chem., 276 (17): 13941-8. [PMID:11278341]

47. Hatem S, Hoyaux D, De Decker V, Appelboom T, Pochet R, Steinfeld S. (2002) Expression of calcium-sensing receptor in human minor salivary glands. Clin Exp Rheumatol., 20: 576-576. [PMID:12175122]

48. Hauache OM, Hu J, Ray K, Xie R, Jacobson KA, Spiegel AM. (2000) Effects of a calcimimetic compound and naturally activating mutations on the human Ca2+ receptor and on Ca2+ receptor/metabotropic glutamate chimeric receptors. Endocrinology, 141 (11): 4156-63. [PMID:11089548]

49. Ho C, Conner DA, Pollak MR, Ladd DJ, Kifor O, Warren HB, Brown EM, Seidman JG, Seidman CE. (1995) A mouse model of human familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism. Nat. Genet., 11 (4): 389-94. [PMID:7493018]

50. Huang C, Handlogten ME, Miller RT. (2002) Parallel activation of phosphatidylinositol 4-kinase and phospholipase C by the extracellular calcium-sensing receptor. J. Biol. Chem., 277 (23): 20293-300. [PMID:11907035]

51. Huang C, Hujer KM, Wu Z, Miller RT. (2004) The Ca2+-sensing receptor couples to Galpha12/13 to activate phospholipase D in Madin-Darby canine kidney cells. Am. J. Physiol., Cell Physiol., 286 (1): C22-30. [PMID:12954603]

52. Itami A, Kato M, Komoto I, Doi R, Hosotani R, Shimada Y, Imamura M. (2001) Human gastrinoma cells express calcium-sensing receptor. Life Sci., 70 (2): 119-29. [PMID:11787938]

53. Janicic N, Soliman E, Pausova Z, Seldin MF, Rivière M, Szpirer J, Szpirer C, Hendy GN. (1995) Mapping of the calcium-sensing receptor gene (CASR) to human chromosome 3q13.3-21 by fluorescence in situ hybridization, and localization to rat chromosome 11 and mouse chromosome 16. Mamm. Genome, 6 (11): 798-801. [PMID:8597637]

54. Kessler A, Faure H, Petrel C, Ruat M, Dauban P, Dodd RH. (2004) N2-benzyl-N1-(1-(1-naphthyl)ethyl)-3-phenylpropane-1,2-diamines and conformationally restrained indole analogues: development of calindol as a new calcimimetic acting at the calcium sensing receptor. Bioorg. Med. Chem. Lett., 14 (12): 3345-9. [PMID:15149704]

55. Kessler A, Faure H, Roussanne MC, Ferry S, Ruat M, Dauban P, Dodd RH. (2004) N(1)-Arylsulfonyl-N(2)-(1-(1-naphthyl)ethyl)-1,2-diaminocyclohexanes: a new class of calcilytic agents acting at the calcium-sensing receptor. Chembiochem, 5 (8): 1131-6. [PMID:15300839]

56. Kifor O, Diaz R, Butters R, Brown EM. (1997) The Ca2+-sensing receptor (CaR) activates phospholipases C, A2, and D in bovine parathyroid and CaR-transfected, human embryonic kidney (HEK293) cells. J. Bone Miner. Res., 12 (5): 715-25. [PMID:9144337]

57. Kifor O, MacLeod RJ, Diaz R, Bai M, Yamaguchi T, Yao T, Kifor I, Brown EM. (2001) Regulation of MAP kinase by calcium-sensing receptor in bovine parathyroid and CaR-transfected HEK293 cells. Am J Physiol Renal Physiol., 280: F291-F302. [PMID:11208605]

58. Komoto I, Kato M, Itami A, Shimada Y, Doi R, Hosotani R, Imamura M. (2003) Expression and function of the calcium-sensing receptor in pancreatic islets and insulinoma cells. Pancreas, 26 (2): 178-84. [PMID:12604917]

59. Komuves L, Oda Y, Tu CL, Chang WH, Ho-Pao CL, Mauro T, Bikle DD. (2002) Epidermal expression of the full-length extracellular calcium-sensing receptor is required for normal keratinocyte differentiation. J. Cell. Physiol., 192 (1): 45-54. [PMID:12115735]

60. Kumar S, Matheny CJ, Hoffman SJ, Marquis RW, Schultz M, Liang X, Vasko JA, Stroup GB, Vaden VR, Haley H et al.. (2010) An orally active calcium-sensing receptor antagonist that transiently increases plasma concentrations of PTH and stimulates bone formation. Bone, 46 (2): 534-42. [PMID:19786130]

61. Kwak JO, Kwak J, Kim HW, Oh KJ, Kim YT, Jung SM, Cha SH. (2005) The extracellular calcium sensing receptor is expressed in mouse mesangial cells and modulates cell proliferation. Exp. Mol. Med., 37 (5): 457-65. [PMID:16264270]

62. Kállay E, Bonner E, Wrba F, Thakker RV, Peterlik M, Cross HS. (2003) Molecular and functional characterization of the extracellular calcium-sensing receptor in human colon cancer cells. Oncol. Res., 13 (12): 551-9. [PMID:12899245]

63. Leach K, Gregory KJ, Kufareva I, Khajehali E, Cook AE, Abagyan R, Conigrave AD, Sexton PM, Christopoulos A. (2016) Towards a structural understanding of allosteric drugs at the human calcium-sensing receptor. Cell Res., 26 (5): 574-92. [PMID:27002221]

64. Leach K, Wen A, Cook AE, Sexton PM, Conigrave AD, Christopoulos A. (2013) Impact of clinically relevant mutations on the pharmacoregulation and signaling bias of the calcium-sensing receptor by positive and negative allosteric modulators. Endocrinology, 154 (3): 1105-16. [PMID:23372019]

65. Letz S, Haag C, Schulze E, Frank-Raue K, Raue F, Hofner B, Mayr B, Schöfl C. (2014) Amino alcohol- (NPS-2143) and quinazolinone-derived calcilytics (ATF936 and AXT914) differentially mitigate excessive signalling of calcium-sensing receptor mutants causing Bartter syndrome Type 5 and autosomal dominant hypocalcemia. PLoS ONE, 9 (12): e115178. [PMID:25506941]

66. Ma JN, Owens M, Gustafsson M, Jensen J, Tabatabaei A, Schmelzer K, Olsson R, Burstein ES. (2011) Characterization of highly efficacious allosteric agonists of the human calcium-sensing receptor. J. Pharmacol. Exp. Ther., 337 (1): 275-84. [PMID:21239511]

67. MacLeod RJ, Chattopadhyay N, Brown EM. (2003) PTHrP stimulated by the calcium-sensing receptor requires MAP kinase activation. Am. J. Physiol. Endocrinol. Metab., 284 (2): E435-42. [PMID:12388158]

68. MacLeod RJ, Yano S, Chattopadhyay N, Brown EM. (2004) Extracellular calcium-sensing receptor transactivates the epidermal growth factor receptor by a triple-membrane-spanning signaling mechanism. Biochem. Biophys. Res. Commun., 320 (2): 455-60. [PMID:15219850]

69. Mantovani G, Corbetta S, Romoli R, Alberti L, Beck-Peccoz P, Spada A. (2001) Absence of thyroid transcription factor-1 expression in human parathyroid and pituitary glands. Mol. Cell. Endocrinol., 182 (1): 13-7. [PMID:11500234]

70. McNeil L, Hobson S, Nipper V, Rodland KD. (1998) Functional calcium-sensing receptor expression in ovarian surface epithelial cells. Am. J. Obstet. Gynecol., 178 (2): 305-13. [PMID:9500491]

71. McNeil SE, Hobson SA, Nipper V, Rodland KD. (1998) Functional calcium-sensing receptors in rat fibroblasts are required for activation of SRC kinase and mitogen-activated protein kinase in response to extracellular calcium. J Biol Chem., 273: 1114-1120. [PMID:9422777]

72. Mitsuma T, Rhue N, Kayama M, Mori Y, Adachi K, Yokoi Y, Ping J, Nogimori T, Hirooka Y. (1999) Distribution of calcium sensing receptor in rats: an immunohistochemical study. Endocr Regul, 33 (2): 55-9. [PMID:10467425]

73. Miyazaki H, Tsubakimoto J, Yasuda K, Takamuro I, Sakurai O, Yanagida T, Hisada Y. (2013) Arylalkylamine compound and process for preparing the same. Patent number: US8362274 B2. Assignee: Mitsubishi Tanabe Pharma Corporation. Priority date: 28/05/2004. Publication date: 29/01/2013.

74. Motoyama HI, Friedman PA. (2002) Calcium-sensing receptor regulation of PTH-dependent calcium absorption by mouse cortical ascending limbs. Am. J. Physiol. Renal Physiol., 283 (3): F399-406. [PMID:12167589]

75. Nagy E, Rigby WF. (1995) Glyceraldehyde-3-phosphate dehydrogenase selectively binds AU-rich RNA in the NAD(+)-binding region (Rossmann fold). J. Biol. Chem., 270 (6): 2755-63. [PMID:7531693]

76. Nemeth EF. (2004) Calcimimetic and calcilytic drugs: just for parathyroid cells?. Cell Calcium, 35 (3): 283-9. [PMID:15200152]

77. Nemeth EF, Delmar EG, Heaton WL, Miller MA, Lambert LD, Conklin RL, Gowen M, Gleason JG, Bhatnagar PK, Fox J. (2001) Calcilytic compounds: potent and selective Ca2+ receptor antagonists that stimulate secretion of parathyroid hormone. J. Pharmacol. Exp. Ther., 299 (1): 323-31. [PMID:11561095]

78. Nemeth EF, Heaton WH, Miller M, Fox J, Balandrin MF, Van Wagenen BC, Colloton M, Karbon W, Scherrer J, Shatzen E et al.. (2004) Pharmacodynamics of the type II calcimimetic compound cinacalcet HCl. J. Pharmacol. Exp. Ther., 308 (2): 627-35. [PMID:14593085]

79. Nemeth EF, Scarpa A. (1986) Cytosolic Ca2+ and the regulation of secretion in parathyroid cells. FEBS Lett., 203: 15-19. [PMID:3755106]

80. Nemeth EF, Steffey ME, Hammerland LG, Hung BC, Van Wagenen BC, DelMar EG, Balandrin MF. (1998) Calcimimetics with potent and selective activity on the parathyroid calcium receptor. Proc. Natl. Acad. Sci. U.S.A., 95 (7): 4040-5. [PMID:9520489]

81. Oda Y, Tu CL, Chang W, Crumrine D, Kömüves L, Mauro T, Elias PM, Bikle DD. (2000) The calcium sensing receptor and its alternatively spliced form in murine epidermal differentiation. J. Biol. Chem., 275 (2): 1183-90. [PMID:10625662]

82. Oda Y, Tu CL, Pillai S, Bikle DD. (1998) The calcium sensing receptor and its alternatively spliced form in keratinocyte differentiation. J. Biol. Chem., 273 (36): 23344-52. [PMID:9722568]

83. Ogata S, Kubota Y, Satoh S, Ito S, Takeuchi H, Ashizuka M, Shirasuna K. (2006) Ca2+ stimulates COX-2 expression through calcium-sensing receptor in fibroblasts. Biochem. Biophys. Res. Commun., 351 (4): 808-14. [PMID:17097611]

84. Ohsu T, Amino Y, Nagasaki H, Yamanaka T, Takeshita S, Hatanaka T, Maruyama Y, Miyamura N, Eto Y. (2010) Involvement of the calcium-sensing receptor in human taste perception. J. Biol. Chem., 285 (2): 1016-22. [PMID:19892707]

85. Olszak IT, Poznansky MC, Evans RH, Olson D, Kos C, Pollak MR, Brown EM, Scadden DT. (2000) Extracellular calcium elicits a chemokinetic response from monocytes in vitro and in vivo. J. Clin. Invest., 105 (9): 1299-305. [PMID:10792005]

86. Peiris D, Pacheco I, Spencer C, MacLeod RJ. (2007) The extracellular calcium-sensing receptor reciprocally regulates the secretion of BMP-2 and the BMP antagonist Noggin in colonic myofibroblasts. Am. J. Physiol. Gastrointest. Liver Physiol., 292 (3): G753-66. [PMID:17138967]

87. Petrel C, Kessler A, Dauban P, Dodd RH, Rognan D, Ruat M. (2004) Positive and negative allosteric modulators of the Ca2+-sensing receptor interact within overlapping but not identical binding sites in the transmembrane domain. J. Biol. Chem., 279 (18): 18990-7. [PMID:14976203]

88. Petrel C, Kessler A, Maslah F, Dauban P, Dodd RH, Rognan D, Ruat M. (2003) Modeling and mutagenesis of the binding site of Calhex 231, a novel negative allosteric modulator of the extracellular Ca(2+)-sensing receptor. J. Biol. Chem., 278 (49): 49487-94. [PMID:14506236]

89. Pi M, Faber P, Ekema G, Jackson PD, Ting A, Wang N, Fontilla-Poole M, Mays RW, Brunden KR, Harrington JJ et al.. (2005) Identification of a novel extracellular cation-sensing G-protein-coupled receptor. J. Biol. Chem., 280 (48): 40201-9. [PMID:16199532]

90. Pi M, Spurney RF, Tu Q, Hinson T, Quarles LD. (2002) Calcium-sensing receptor activation of rho involves filamin and rho-guanine nucleotide exchange factor. Endocrinology, 143 (10): 3830-8. [PMID:12239094]

91. Quinn SJ, Ye CP, Diaz R, Kifor O, Bai M, Vassilev P, Brown E. (1997) The Ca2+-sensing receptor: a target for polyamines. Am. J. Physiol., 273 (4): C1315-23. [PMID:9357776]

92. Remy C, Kirchhoff P, Hafner P, Busque SM, Müeller MK, Geibel JP, Wagner CA. (2007) Stimulatory pathways of the Calcium-sensing receptor on acid secretion in freshly isolated human gastric glands. Cell. Physiol. Biochem., 19 (1-4): 33-42. [PMID:17310098]

93. Riccardi D, Hall AE, Chattopadhyay N, Xu JZ, Brown EM, Hebert SC. (1998) Localization of the extracellular Ca2+/polyvalent cation-sensing protein in rat kidney. Am. J. Physiol., 274 (3): F611-22. [PMID:9530279]

94. Riccardi D, Park J, Lee WS, Gamba G, Brown EM, Hebert SC. (1995) Cloning and functional expression of a rat kidney extracellular calcium/polyvalent cation-sensing receptor. Proc. Natl. Acad. Sci. U.S.A., 92 (1): 131-5. [PMID:7816802]

95. Riccardi D, Traebert M, Ward DT, Kaissling B, Biber J, Hebert SC, Murer H. (2000) Dietary phosphate and parathyroid hormone alter the expression of the calcium-sensing receptor (CaR) and the Na+-dependent Pi transporter (NaPi-2) in the rat proximal tubule. Pflugers Arch., 441: 379-387. [PMID:11211126]

96. Rodriguez L, Tu C, Cheng Z, Chen TH, Bikle D, Shoback D, Chang W. (2005) Expression and functional assessment of an alternatively spliced extracellular Ca2+-sensing receptor in growth plate chondrocytes. Endocrinology, 146 (12): 5294-303. [PMID:16166224]

97. Rogers KV, Dunn CK, Hebert SC, Brown EM. (1997) Localization of calcium receptor mRNA in the adult rat central nervous system by in situ hybridization. Brain Res., 744: 47-56. [PMID:9030412]

98. Rutten MJ, Bacon KD, Marlink KL, Stoney M, Meichsner CL, Lee FP, Hobson SA, Rodland KD, Sheppard BC, Trunkey DD et al.. (1999) Identification of a functional Ca2+-sensing receptor in normal human gastric mucous epithelial cells. Am. J. Physiol., 277 (3): G662-70. [PMID:10484392]

99. Rácz GZ, Kittel A, Riccardi D, Case RM, Elliott AC, Varga G. (2002) Extracellular calcium sensing receptor in human pancreatic cells. Gut, 51 (5): 705-11. [PMID:12377811]

100. Sanders JL, Chattopadhyay N, Kifor O, Yamaguchi T, Brown EM. (2000) Extracellular calcium-sensing receptor (CaR) expression and its potential role in parathyroid hormone-related peptide (PTHrP) secretion in the H-500 rat Leydig cell model of humoral hypercalcemia of malignancy. Biochem. Biophys. Res. Commun., 269 (2): 427-32. [PMID:10708570]

101. Sanders JL, Chattopadhyay N, Kifor O, Yamaguchi T, Brown EM. (2001) Ca(2+)-sensing receptor expression and PTHrP secretion in PC-3 human prostate cancer cells. Am. J. Physiol. Endocrinol. Metab., 281 (6): E1267-74. [PMID:11701443]

102. Sanders JL, Chattopadhyay N, Kifor O, Yamaguchi T, Butters RR, Brown EM. (2000) Extracellular calcium-sensing receptor expression and its potential role in regulating parathyroid hormone-related peptide secretion in human breast cancer cell lines. Endocrinology, 141: 4357-4364. [PMID:11108243]

103. Sands JM, Naruse M, Baum M, Jo I, Hebert SC, Brown EM, Harris HW. (1997) Apical extracellular calcium/polyvalent cation-sensing receptor regulates vasopressin-elicited water permeability in rat kidney inner medullary collecting duct. J Clin Invest., 99: 1399-1405. [PMID:9077550]

104. Shalhoub V, Grisanti M, Padagas J, Scully S, Rattan A, Qi M, Varnum B, Vezina C, Lacey D, Martin D. (2003) In vitro studies with the calcimimetic, cinacalcet HCl, on normal human adult osteoblastic and osteoclastic cells. Crit. Rev. Eukaryot. Gene Expr., 13 (2-4): 89-106. [PMID:14696958]

105. Shcherbakova I, Huang G, Geoffroy OJ, Nair SK, Swierczek K, Balandrin MF, Fox J, Heaton WL, Conklin RL. (2005) Design, new synthesis, and calcilytic activity of substituted 3H-pyrimidin-4-ones. Bioorg. Med. Chem. Lett., 15 (10): 2537-40. [PMID:15863312]

106. Sheinin Y, Kállay E, Wrba F, Kriwanek S, Peterlik M, Cross HS. (2000) Immunocytochemical localization of the extracellular calcium-sensing receptor in normal and malignant human large intestinal mucosa. J. Histochem. Cytochem., 48 (5): 595-602. [PMID:10769043]

107. Shinagawa Y, Inoue T, Katsushima T, Kiguchi T, Ikenogami T, Ogawa N, Fukuda K, Hirata K, Harada K, Takagi M et al.. (2011) Discovery of a potent and short-acting oral calcilytic with a pulsatile secretion of parathyroid hormone. ACS Med Chem Lett, 2 (3): 238-42. [PMID:24900301]

108. Tfelt-Hansen J, Chattopadhyay N, Yano S, Kanuparthi D, Rooney P, Schwarz P, Brown EM. (2004) Calcium-sensing receptor induces proliferation through p38 mitogen-activated protein kinase and phosphatidylinositol 3-kinase but not extracellularly regulated kinase in a model of humoral hypercalcemia of malignancy. Endocrinology, 145 (3): 1211-7. [PMID:14645111]

109. Turksen K, Troy TC. (2003) Overexpression of the calcium sensing receptor accelerates epidermal differentiation and permeability barrier formation in vivo. Mech. Dev., 120 (6): 733-44. [PMID:12834872]

110. VanHouten J, Dann P, McGeoch G, Brown EM, Krapcho K, Neville M, Wysolmerski JJ. (2004) The calcium-sensing receptor regulates mammary gland parathyroid hormone-related protein production and calcium transport. J Clin Invest., 113: 598-608. [PMID:14966569]

111. Wada M, Nagano N, Furuya Y, Chin J, Nemeth EF, Fox J. (2000) Calcimimetic NPS R-568 prevents parathyroid hyperplasia in rats with severe secondary hyperparathyroidism. Kidney Int., 57 (1): 50-8. [PMID:10620187]

112. Walter S, Baruch A, Dong J, Tomlinson JE, Alexander ST, Janes J, Hunter T, Yin Q, Maclean D, Bell G et al.. (2013) Pharmacology of AMG 416 (Velcalcetide), a novel peptide agonist of the calcium-sensing receptor, for the treatment of secondary hyperparathyroidism in hemodialysis patients. J. Pharmacol. Exp. Ther., 346 (2): 229-40. [PMID:23674604]

113. Wang M, Yao Y, Kuang D, Hampson DR. (2006) Activation of family C G-protein-coupled receptors by the tripeptide glutathione. J. Biol. Chem., 281 (13): 8864-70. [PMID:16455645]

114. Wang R, Xu C, Zhao W, Zhang J, Cao K, Yang B, Wu L. (2003) Calcium and polyamine regulated calcium-sensing receptors in cardiac tissues. Eur. J. Biochem., 270 (12): 2680-8. [PMID:12787035]

115. Wang Y, Awumey EK, Chatterjee PK, Somasundaram C, Bian K, Rogers KV, Dunn C, Bukoski RD. (2003) Molecular cloning and characterization of a rat sensory nerve Ca2+-sensing receptor. Am J Physiol Cell Physiol., 285: C64-C75. [PMID:12637267]

116. Widler L, Altmann E, Beerli R, Breitenstein W, Bouhelal R, Buhl T, Gamse R, Gerspacher M, Halleux C, John MR et al.. (2010) 1-Alkyl-4-phenyl-6-alkoxy-1H-quinazolin-2-ones: a novel series of potent calcium-sensing receptor antagonists. J. Med. Chem., 53 (5): 2250-63. [PMID:20158186]

117. Yamaguchi T, Chattopadhyay N, Kifor O, Brown EM. (1998) Extracellular calcium (Ca2+(o))-sensing receptor in a murine bone marrow-derived stromal cell line (ST2): potential mediator of the actions of Ca2+(o) on the function of ST2 cells. Endocrinology, 139 (8): 3561-8. [PMID:9681508]

118. Yamaguchi T, Chattopadhyay N, Kifor O, Butters Jr RR, Sugimoto T, Brown EM. (1998) Mouse osteoblastic cell line (MC3T3-E1) expresses extracellular calcium (Ca2+o)-sensing receptor and its agonists stimulate chemotaxis and proliferation of MC3T3-E1 cells. J. Bone Miner. Res., 13 (10): 1530-8. [PMID:9783541]

119. Yamaguchi T, Chattopadhyay N, Kifor O, Ye C, Vassilev PM, Sanders JL, Brown EM. (2001) Expression of extracellular calcium-sensing receptor in human osteoblastic MG-63 cell line. Am. J. Physiol., Cell Physiol., 280 (2): C382-93. [PMID:11208534]

120. Yamaguchi T, Yamauchi M, Sugimoto T, Chauhan D, Anderson KC, Brown EM, Chihara K. (2002) The extracellular calcium Ca2+o-sensing receptor is expressed in myeloma cells and modulates cell proliferation. Biochem. Biophys. Res. Commun., 299 (4): 532-8. [PMID:12459170]

121. Yamaguchi T, Ye C, Chattopadhyay N, Sanders JL, Vassilev PM, Brown EM. (2000) Enhanced expression of extracellular calcium sensing receptor in monocyte-differentiated versus undifferentiated HL-60 cells: potential role in regulation of a nonselective cation channel. Calcif. Tissue Int., 66 (5): 375-82. [PMID:10773108]

122. Yang W, Wang Y, Roberge JY, Ma Z, Liu Y, Michael Lawrence R, Rotella DP, Seethala R, Feyen JH, Dickson JK. (2005) Discovery and structure-activity relationships of 2-benzylpyrrolidine-substituted aryloxypropanols as calcium-sensing receptor antagonists. Bioorg Med Chem Lett, 15: 1225-1228. [PMID:15686947]

123. Yano S, Macleod RJ, Chattopadhyay N, Tfelt-Hansen J, Kifor O, Butters RR, Brown EM. (2004) Calcium-sensing receptor activation stimulates parathyroid hormone-related protein secretion in prostate cancer cells: role of epidermal growth factor receptor transactivation. Bone, 35 (3): 664-72. [PMID:15336602]

124. Ye C, Chattopadhyay N, Brown EM, Vassilev PM. (2000) Defective extracellular calcium (Ca(o))-sensing receptor (CaR)-mediated stimulation of a Ca(2+)-activated potassium channel in glioblastoma cells transfected with a dominant negative CaR. Brain Res Mol Brain Res., 80: 177-187. [PMID:11038250]

125. Ye C, Rogers K, Bai M, Quinn SJ, Brown EM, Vassilev PM. (1996) Agonists of the Ca(2+)-sensing receptor (CaR) activate nonselective cation channels in HEK293 cells stably transfected with the human CaR. Biochem. Biophys. Res. Commun., 226 (2): 572-9. [PMID:8806675]

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