5-ht<sub>1e</sub> receptor | 5-Hydroxytryptamine receptors | IUPHAR Guide to IMMUNOPHARMACOLOGY

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5-ht1e receptor

  Target has curated data in GtoImmuPdb

Target id: 4

Nomenclature: 5-ht1e receptor

Family: 5-Hydroxytryptamine receptors

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 A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 365 6q14-q15 HTR1E 5-hydroxytryptamine receptor 1E 11-12,24
Previous and Unofficial Names
5-HT1Eα | 5-HT1E | 5-hydroxytryptamine (serotonin) receptor 1E, G protein-coupled
Database Links
Specialist databases
GPCRDB 5ht1e_human (Hs)
Other databases
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Natural/Endogenous Ligands
5-hydroxytryptamine
tryptamine
Comments: Endogenous ligand tryptamine is a weak agonist

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
[3H]5-HT Hs Full agonist 8.1 – 8.2 pKd 12,15
pKd 8.1 – 8.2 (Kd 7.94x10-9 – 6.31x10-9 M) [12,15]
BRL-54443 Hs Full agonist 8.7 pKi 5
pKi 8.7 [5]
5-hydroxytryptamine Hs Full agonist 8.0 – 8.2 pKi 1,4,7,12
pKi 8.0 – 8.2 [1,4,7,12]
asenapine Hs Full agonist 8.0 pKi 18
pKi 8.0 [18]
naratriptan Hs Full agonist 7.7 pKi 14
pKi 7.7 [14]
zolmitriptan Hs Full agonist 7.7 pKi 14
pKi 7.7 [14]
lysergol Hs Full agonist 7.4 pKi 15
pKi 7.4 [15]
ergometrine Hs Full agonist 7.3 pKi 4
pKi 7.3 [4]
eletriptan Hs Full agonist 7.2 pKi 14
pKi 7.2 [14]
α-methyl-5-HT Hs Full agonist 6.9 – 7.0 pKi 1,4
pKi 6.9 – 7.0 [1,4]
rizatriptan Hs Full agonist 6.8 pKi 14
pKi 6.8 [14]
5-BODMT Hs Agonist 6.6 pKi 10
pKi 6.6 (Ki 2.4x10-7 M) [10]
clozapine Hs Full agonist 6.4 pKi 18
pKi 6.4 [18]
ziprasidone Hs Full agonist 6.4 pKi 18
pKi 6.4 [18]
EMDT Hs Full agonist 6.3 pKi 8
pKi 6.3 [8]
5-fluorotryptamine Hs Full agonist 6.3 pKi 4
pKi 6.3 [4]
ergotamine Hs Full agonist 6.2 – 6.3 pKi 1,12
pKi 6.2 – 6.3 [1,12]
5-MeO-DMT Hs Full agonist 6.1 – 6.3 pKi 1,7
pKi 6.1 – 6.3 [1,7]
2-methyl-5-HT Hs Full agonist 6.1 pKi 1
pKi 6.1 [1]
tryptamine Hs Full agonist 5.6 – 6.5 pKi 1,4,7
pKi 5.6 – 6.5 [1,4,7]
donitriptan Hs Full agonist 5.9 pKi 9
pKi 5.9 [9]
quetiapine Hs Full agonist 5.9 pKi 18
pKi 5.9 [18]
5-MeOT Hs Full agonist 5.5 – 6.2 pKi 1,4,7,15
pKi 5.5 – 6.2 [1,4,7,15]
LY344864 Hs Full agonist 5.8 pKi 16
pKi 5.8 [16]
olanzapine Hs Full agonist 5.7 pKi 18
pKi 5.7 [18]
sumatriptan Hs Full agonist 5.6 – 5.8 pKi 1,4,12,14-15
pKi 5.6 – 5.8 [1,4,12,14-15]
DOI Hs Full agonist 5.5 – 5.8 pKi 1,4
pKi 5.5 – 5.8 [1,4]
xanomeline Hs Full agonist 5.6 pKi 23
pKi 5.6 [23]
dihydroergotamine Hs Full agonist 5.6 pKi 15
pKi 5.6 [15]
8-OH-DPAT Hs Full agonist 5.5 pKi 1,4
pKi 5.5 [1,4]
GR 127935 Hs Partial agonist 5.4 pKi 17
pKi 5.4 [17]
m-chlorophenylpiperazine Hs Partial agonist 5.4 pKi 4
pKi 5.4 [4]
5-CT Hs Full agonist 5.1 – 5.5 pKi 1,4,12,15
pKi 5.1 – 5.5 [1,4,12,15]
TFMPP Hs Full agonist 5.2 – 5.4 pKi 1,4,15
pKi 5.2 – 5.4 [1,4,15]
BRL-15572 Hs Partial agonist 5.2 pKi 17
pKi 5.2 [17]
Agonist Comments
Compared to other family members, BRL-54443 is selective for 5-HT1e and 5-HT1F receptors [5].
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
methylergonovine Hs Antagonist 7.0 – 7.2 pKi 1,7
pKi 7.0 – 7.2 [1,7]
1-naphthylpiperazine Hs Antagonist 6.7 – 7.0 pKi 1,4,15
pKi 6.7 – 7.0 [1,4,15]
methiothepin Hs Antagonist 6.7 – 7.0 pKi 1,4,12,15
pKi 6.7 – 7.0 [1,4,12,15]
methysergide Hs Antagonist 6.5 – 6.8 pKi 1,4,7,12,15
pKi 6.5 – 6.8 [1,4,7,12,15]
zotepine Hs Antagonist 6.5 pKi 18
pKi 6.5 [18]
sertindole Hs Antagonist 6.4 pKi 18
pKi 6.4 [18]
9-OH-risperidone Hs Antagonist 6.0 pKi 18
pKi 6.0 [18]
risperidone Hs Antagonist 5.9 pKi 18
pKi 5.9 [18]
yohimbine Hs Antagonist 5.9 pKi 1
pKi 5.9 [1]
metergoline Hs Antagonist 5.6 – 6.1 pKi 4,12,15
pKi 5.6 – 6.1 [4,12,15]
fluspirilene Hs Antagonist 5.6 pKi 18
pKi 5.6 [18]
rauwolscine Hs Antagonist 5.4 – 5.5 pKi 4,15
pKi 5.4 – 5.5 [4,15]
Immunopharmacology Comments
The expression of 5-HT1e receptors on immune cells indicates that it plays some part in immune/inflammatory responses [22].
Cell Type Associations
Immuno Cell Type:  Granulocytes
Cell Ontology Term:   mature eosinophil (CL:0000041)
Comment:  Expressed by eosinophils.
References:  22
Immuno Cell Type:  Dendritic cells
Cell Ontology Term:   dendritic cell (CL:0000451)
Comment:  Involved in DC chemotaxis.
References:  3,22
Immuno Cell Type:  Macrophages & monocytes
Cell Ontology Term:   monocyte (CL:0000576)
macrophage (CL:0000235)
References:  3,19,22
Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family Adenylate cyclase inhibition
Comments:  At higher concentrations, 5-HT can potentiate forskolin-stimulated cAMP accumulation [2].
References:  2
Tissue Distribution
Putamen > frontal cortex, globus pallidus.
Species:  Human
Technique:  Radioligand binding.
References:  13
Cortical areas, caudate, putamen, amygdala.
Species:  Human
Technique:  in situ hybridisation.
References:  6
Functional Assays
Measurement of cAMP levels in a murine fibroblast cell line transfected with the human 5-HT1e receptor.
Species:  Human
Tissue:  Murine fibroblast cell line.
Response measured:  Inhibition of cAMP accumulation.
References:  24
Measurement of cAMP levels in HEK 293 cells transfected with the human 5-HT1e receptor.
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  Inhibition of cAMP accumulation.
References:  12
Measurement of cAMP levels in BS-C-1 cells transfected with the human 5-HT1e receptor.
Species:  Human
Tissue:  BS-C-1 cells
Response measured:  PTX-sensitive inhibition of cAMP accumulation.
References:  2
Gene Expression and Pathophysiology Comments
There is also evidence to suggest that the 5-ht5a is not found in lymphocytes [21].
Biologically Significant Variant Comments
There have been no receptor variants reported. This suggests high evolutionary conservation of the 5-ht1e receptor [20].

References

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1. Adham N, Kao HT, Schecter LE, Bard J, Olsen M, Urquhart D, Durkin M, Hartig PR, Weinshank RL, Branchek TA. (1993) Cloning of another human serotonin receptor (5-HT1F): a fifth 5-HT1 receptor subtype coupled to the inhibition of adenylate cyclase. Proc. Natl. Acad. Sci. U.S.A., 90 (2): 408-12. [PMID:8380639]

2. Adham N, Vaysse PJ, Weinshank RL, Branchek TA. (1994) The cloned human 5-HT1E receptor couples to inhibition and activation of adenylyl cyclase via two distinct pathways in transfected BS-C-1 cells. Neuropharmacology, 33 (3-4): 403-10. [PMID:7984278]

3. Ahern GP. (2011) 5-HT and the immune system. Curr Opin Pharmacol, 11 (1): 29-33. [PMID:21393060]

4. Bai F, Yin T, Johnstone EM, Su C, Varga G, Little SP, Nelson DL. (2004) Molecular cloning and pharmacological characterization of the guinea pig 5-HT1E receptor. Eur. J. Pharmacol., 484 (2-3): 127-39. [PMID:14744596]

5. Brown AM, Avenell K, Young TJ, Ho M, Porter RA, Vimal M, Middlemiss DN. (1998) BRL 54443, a potent agonist with selectivity for human cloned 5-HT1E and 5-HT1F receptors. British Journal of Pharmacology, 123 (1): 233.

6. Bruinvels AT, Landwehrmeyer B, Gustafson EL, Durkin MM, Mengod G, Branchek TA, Hoyer D, Palacios JM. (1994) Localization of 5-HT1B, 5-HT1D alpha, 5-HT1E and 5-HT1F receptor messenger RNA in rodent and primate brain. Neuropharmacology, 33 (3-4): 367-86. [PMID:7984275]

7. Dukat M, Smith C, Herrick-Davis K, Teitler M, Glennon RA. (2004) Binding of tryptamine analogs at h5-HT1E receptors: a structure-affinity investigation. Bioorg. Med. Chem., 12 (10): 2545-52. [PMID:15110837]

8. Glennon RA, Lee M, Rangisetty JB, Dukat M, Roth BL, Savage JE, McBride A, Rauser L, Hufeisen S, Lee DK. (2000) 2-Substituted tryptamines: agents with selectivity for 5-HT(6) serotonin receptors. J. Med. Chem., 43 (5): 1011-8. [PMID:10715164]

9. John GW, Pauwels PJ, Perez M, Halazy S, Le Grand B, Verscheure Y, Valentin JP, Palmier C, Wurch T, Chopin P et al.. (1999) F 11356, a novel 5-hydroxytryptamine (5-HT) derivative with potent, selective, and unique high intrinsic activity at 5-HT1B/1D receptors in models relevant to migraine. J. Pharmacol. Exp. Ther., 290 (1): 83-95. [PMID:10381763]

10. Klein MT, Dukat M, Glennon RA, Teitler M. (2011) Toward selective drug development for the human 5-hydroxytryptamine 1E receptor: a comparison of 5-hydroxytryptamine 1E and 1F receptor structure-affinity relationships. J. Pharmacol. Exp. Ther., 337 (3): 860-7. [PMID:21422162]

11. Levy FO, Holtgreve-Grez H, Taskén K, Solberg R, Ried T, Gudermann T. (1994) Assignment of the gene encoding the 5-HT1E serotonin receptor (S31) (locus HTR1E) to human chromosome 6q14-q15. Genomics, 22 (3): 637-40. [PMID:8001977]

12. McAllister G, Charlesworth A, Snodin C, Beer MS, Noble AJ, Middlemiss DN, Iversen LL, Whiting P. (1992) Molecular cloning of a serotonin receptor from human brain (5HT1E): a fifth 5HT1-like subtype. Proc. Natl. Acad. Sci. U.S.A., 89 (12): 5517-21. [PMID:1608964]

13. Miller KJ, Teitler M. (1992) Quantitative autoradiography of 5-CT-sensitive (5-HT1D) and 5-CT-insensitive (5-HT1E) serotonin receptors in human brain. Neurosci. Lett., 136 (2): 223-6. [PMID:1641195]

14. Napier C, Stewart M, Melrose H, Hopkins B, McHarg A, Wallis R. (1999) Characterisation of the 5-HT receptor binding profile of eletriptan and kinetics of [3H]eletriptan binding at human 5-HT1B and 5-HT1D receptors. Eur. J. Pharmacol., 368 (2-3): 259-68. [PMID:10193663]

15. Parker EM, Izzarelli DG, Lewis-Higgins L, Palmer D, Shapiro RA. (1996) Two amino acid differences in the sixth transmembrane domain are partially responsible for the pharmacological differences between the 5-HT1D beta and 5-HT1E 5-hydroxytryptamine receptors. J. Neurochem., 67 (5): 2096-103. [PMID:8863519]

16. Phebus LA, Johnson KW, Zgombick JM, Gilbert PJ, Van Belle K, Mancuso V, Nelson DL, Calligaro DO, Kiefer Jr AD, Branchek TA et al.. (1997) Characterization of LY344864 as a pharmacological tool to study 5-HT1F receptors: binding affinities, brain penetration and activity in the neurogenic dural inflammation model of migraine. Life Sci., 61 (21): 2117-26. [PMID:9395253]

17. Price GW, Burton MJ, Collin LJ, Duckworth M, Gaster L, Göthert M, Jones BJ, Roberts C, Watson JM, Middlemiss DN. (1997) SB-216641 and BRL-15572--compounds to pharmacologically discriminate h5-HT1B and h5-HT1D receptors. Naunyn Schmiedebergs Arch. Pharmacol., 356 (3): 312-20. [PMID:9303567]

18. Schotte A, Janssen PF, Gommeren W, Luyten WH, Van Gompel P, Lesage AS, De Loore K, Leysen JE. (1996) Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding. Psychopharmacology (Berl.), 124 (1-2): 57-73. [PMID:8935801]

19. Shajib MS, Khan WI. (2015) The role of serotonin and its receptors in activation of immune responses and inflammation. Acta Physiol (Oxf), 213 (3): 561-74. [PMID:25439045]

20. Shimron-Abarbanell D, Nöthen MM, Erdmann J, Propping P. (1995) Lack of genetically determined structural variants of the human serotonin-1E (5-HT1E) receptor protein points to its evolutionary conservation. Brain Res. Mol. Brain Res., 29 (2): 387-90. [PMID:7609628]

21. Stefulj J, Jernej B, Cicin-Sain L, Rinner I, Schauenstein K. (2000) mRNA expression of serotonin receptors in cells of the immune tissues of the rat. Brain Behav. Immun., 14 (3): 219-24. [PMID:10970681]

22. Wang SJ, Sharkey KA, McKay DM. (2018) Modulation of the immune response by helminths: a role for serotonin?. Biosci. Rep., 38 (5). DOI: 10.1042/BSR20180027 [PMID:30177522]

23. Watson J, Brough S, Coldwell MC, Gager T, Ho M, Hunter AJ, Jerman J, Middlemiss DN, Riley GJ, Brown AM. (1998) Functional effects of the muscarinic receptor agonist, xanomeline, at 5-HT1 and 5-HT2 receptors. Br. J. Pharmacol., 125 (7): 1413-20. [PMID:9884068]

24. Zgombick JM, Schechter LE, Macchi M, Hartig PR, Branchek TA, Weinshank RL. (1992) Human gene S31 encodes the pharmacologically defined serotonin 5-hydroxytryptamine1E receptor. Mol. Pharmacol., 42 (2): 180-5. [PMID:1513320]

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