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5-ht1e receptor

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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 4

Nomenclature: 5-ht1e receptor

Family: 5-Hydroxytryptamine receptors

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 7 365 6q14.3 HTR1E 5-hydroxytryptamine receptor 1E 11-12,24
Previous and Unofficial Names Click here for help
5-HT1Eα | 5-HT1E | 5-hydroxytryptamine (serotonin) receptor 1E, G protein-coupled
Database Links Click here for help
Specialist databases
GPCRDB 5ht1e_human (Hs)
Other databases
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Natural/Endogenous Ligands Click here for help
5-hydroxytryptamine
tryptamine
Comments: Endogenous ligand tryptamine is a weak agonist

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
[3H]5-HT Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive 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 Small molecule or natural product Click here for species-specific activity table Hs Full agonist 8.7 pKi 5
pKi 8.7 [5]
5-hydroxytryptamine Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Hs Full agonist 8.0 – 8.2 pKi 1,4,7,12
pKi 8.0 – 8.2 [1,4,7,12]
asenapine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Full agonist 8.0 pKi 18
pKi 8.0 [18]
naratriptan Small molecule or natural product Approved drug Click here for species-specific activity table Hs Full agonist 7.7 pKi 14
pKi 7.7 [14]
zolmitriptan Small molecule or natural product Approved drug Click here for species-specific activity table Hs Full agonist 7.7 pKi 14
pKi 7.7 [14]
lysergol Small molecule or natural product Click here for species-specific activity table Hs Full agonist 7.4 pKi 15
pKi 7.4 [15]
ergometrine Small molecule or natural product Approved drug Hs Full agonist 7.3 pKi 4
pKi 7.3 [4]
eletriptan Small molecule or natural product Approved drug Click here for species-specific activity table Hs Full agonist 7.2 pKi 14
pKi 7.2 [14]
α-methyl-5-HT Small molecule or natural product Click here for species-specific activity table Hs Full agonist 6.9 – 7.0 pKi 1,4
pKi 6.9 – 7.0 [1,4]
rizatriptan Small molecule or natural product Approved drug Click here for species-specific activity table Hs Full agonist 6.8 pKi 14
pKi 6.8 [14]
5-BODMT Small molecule or natural product Click here for species-specific activity table Hs Agonist 6.6 pKi 10
pKi 6.6 (Ki 2.4x10-7 M) [10]
clozapine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Full agonist 6.4 pKi 18
pKi 6.4 [18]
ziprasidone Small molecule or natural product Approved drug Click here for species-specific activity table Hs Full agonist 6.4 pKi 18
pKi 6.4 [18]
EMDT Small molecule or natural product Click here for species-specific activity table Hs Full agonist 6.3 pKi 8
pKi 6.3 [8]
5-fluorotryptamine Small molecule or natural product Hs Full agonist 6.3 pKi 4
pKi 6.3 [4]
ergotamine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 6.2 – 6.3 pKi 1,12
pKi 6.2 – 6.3 [1,12]
5-MeO-DMT Small molecule or natural product Click here for species-specific activity table Hs Full agonist 6.1 – 6.3 pKi 1,7
pKi 6.1 – 6.3 [1,7]
2-methyl-5-HT Small molecule or natural product Click here for species-specific activity table Hs Full agonist 6.1 pKi 1
pKi 6.1 [1]
tryptamine Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Hs Full agonist 5.6 – 6.5 pKi 1,4,7
pKi 5.6 – 6.5 [1,4,7]
donitriptan Small molecule or natural product Click here for species-specific activity table Hs Full agonist 5.9 pKi 9
pKi 5.9 [9]
quetiapine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Full agonist 5.9 pKi 18
pKi 5.9 [18]
5-MeOT Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 5.5 – 6.2 pKi 1,4,7,15
pKi 5.5 – 6.2 [1,4,7,15]
LY344864 Small molecule or natural product Click here for species-specific activity table Hs Full agonist 5.8 pKi 16
pKi 5.8 [16]
olanzapine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Full agonist 5.7 pKi 18
pKi 5.7 [18]
sumatriptan Small molecule or natural product Approved drug Click here for species-specific activity table Hs Full agonist 5.6 – 5.8 pKi 1,4,12,14-15
pKi 5.6 – 5.8 [1,4,12,14-15]
DOI Small molecule or natural product Click here for species-specific activity table Hs Full agonist 5.5 – 5.8 pKi 1,4
pKi 5.5 – 5.8 [1,4]
xanomeline Small molecule or natural product Click here for species-specific activity table Hs Full agonist 5.6 pKi 23
pKi 5.6 [23]
dihydroergotamine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 5.6 pKi 15
pKi 5.6 [15]
8-OH-DPAT Small molecule or natural product Click here for species-specific activity table Hs Full agonist 5.5 pKi 1,4
pKi 5.5 [1,4]
GR 127935 Small molecule or natural product Click here for species-specific activity table Hs Partial agonist 5.4 pKi 17
pKi 5.4 [17]
m-chlorophenylpiperazine Small molecule or natural product Click here for species-specific activity table Hs Partial agonist 5.4 pKi 4
pKi 5.4 [4]
5-CT Small molecule or natural product Click here for species-specific activity table Hs Full agonist 5.1 – 5.5 pKi 1,4,12,15
pKi 5.1 – 5.5 [1,4,12,15]
TFMPP Small molecule or natural product Click here for species-specific activity table Hs Full agonist 5.2 – 5.4 pKi 1,4,15
pKi 5.2 – 5.4 [1,4,15]
BRL-15572 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand 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 Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 7.0 – 7.2 pKi 1,7
pKi 7.0 – 7.2 [1,7]
1-naphthylpiperazine Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.7 – 7.0 pKi 1,4,15
pKi 6.7 – 7.0 [1,4,15]
methiothepin Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.7 – 7.0 pKi 1,4,12,15
pKi 6.7 – 7.0 [1,4,12,15]
methysergide Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 6.5 – 6.8 pKi 1,4,7,12,15
pKi 6.5 – 6.8 [1,4,7,12,15]
zotepine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 6.5 pKi 18
pKi 6.5 [18]
sertindole Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 6.4 pKi 18
pKi 6.4 [18]
9-OH-risperidone Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.0 pKi 18
pKi 6.0 [18]
risperidone Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 5.9 pKi 18
pKi 5.9 [18]
yohimbine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 5.9 pKi 1
pKi 5.9 [1]
metergoline Small molecule or natural product Click here for species-specific activity table Hs Antagonist 5.6 – 6.1 pKi 4,12,15
pKi 5.6 – 6.1 [4,12,15]
fluspirilene Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 5.6 pKi 18
pKi 5.6 [18]
rauwolscine Small molecule or natural product Click here for species-specific activity table 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 Click here for help
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 Click here for help
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 Click here for help
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. Br J Pharmacol., 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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