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. 

Contents

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 (serotonin) receptor 1E, G protein-coupled 9-10,20
Previous and Unofficial Names
5-HT1Eα
5-HT1E
5-hydroxytryptamine (serotonin) receptor 1E
Database Links
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
GPCRDB
GeneCards
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
OMIM
PharmGKB Gene
PhosphoSitePlus
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene Hs.
UniProtKB
Wikipedia
Natural/Endogenous Ligands
5-HT
Comments: Endogenous ligand tryptamine is a weak agonist
Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[3H]5-HT Hs Full agonist 8.1 – 8.2 pKd 10,13
pKd 8.1 – 8.2 (Kd 6.31x10-9 – 7.94x10-9 M) [10,13]
BRL-54443 Hs Full agonist 8.7 pKi 4
pKi 8.7 [4]
5-HT Hs Full agonist 8.0 – 8.2 pKi 1,3,6,10
pKi 8.0 – 8.2 [1,3,6,10]
asenapine Hs Full agonist 8.0 pKi 16
pKi 8.0 [16]
naratriptan Hs Full agonist 7.7 pKi 12
pKi 7.7 [12]
zolmitriptan Hs Full agonist 7.7 pKi 12
pKi 7.7 [12]
lysergol Hs Full agonist 7.4 pKi 13
pKi 7.4 [13]
ergometrine Hs Full agonist 7.3 pKi 3
pKi 7.3 [3]
eletriptan Hs Full agonist 7.2 pKi 12
pKi 7.2 [12]
α-methyl-5-HT Hs Full agonist 6.9 – 7.0 pKi 1,3
pKi 6.9 – 7.0 [1,3]
rizatriptan Hs Full agonist 6.8 pKi 12
pKi 6.8 [12]
ziprasidone Hs Full agonist 6.4 pKi 16
pKi 6.4 [16]
clozapine Hs Full agonist 6.4 pKi 16
pKi 6.4 [16]
EMDT Hs Full agonist 6.3 pKi 7
pKi 6.3 [7]
5-fluorotryptamine Hs Full agonist 6.3 pKi 3
pKi 6.3 [3]
ergotamine Hs Full agonist 6.2 – 6.3 pKi 1,10
pKi 6.2 – 6.3 [1,10]
5-MeO-DMT Hs Full agonist 6.1 – 6.3 pKi 1,6
pKi 6.1 – 6.3 [1,6]
2-methyl-5-HT Hs Full agonist 6.1 pKi 1
pKi 6.1 [1]
tryptamine Hs Full agonist 5.6 – 6.5 pKi 1,3,6
pKi 5.6 – 6.5 [1,3,6]
quetiapine Hs Full agonist 5.9 pKi 16
pKi 5.9 [16]
donitriptan Hs Full agonist 5.9 pKi 8
pKi 5.9 [8]
5-MeOT Hs Full agonist 5.5 – 6.2 pKi 1,3,6,13
pKi 5.5 – 6.2 [1,3,6,13]
LY344864 Hs Full agonist 5.8 pKi 14
pKi 5.8 [14]
sumatriptan Hs Full agonist 5.6 – 5.8 pKi 1,3,10,12-13
pKi 5.6 – 5.8 [1,3,10,12-13]
olanzapine Hs Full agonist 5.7 pKi 16
pKi 5.7 [16]
DOI Hs Full agonist 5.5 – 5.8 pKi 1,3
pKi 5.5 – 5.8 [1,3]
xanomeline Hs Full agonist 5.6 pKi 19
pKi 5.6 [19]
dihydroergotamine Hs Full agonist 5.6 pKi 13
pKi 5.6 [13]
8-OH-DPAT Hs Full agonist 5.5 pKi 1,3
pKi 5.5 [1,3]
GR-127935 Hs Partial agonist 5.4 pKi 15
pKi 5.4 [15]
m-CPP Hs Partial agonist 5.4 pKi 3
pKi 5.4 [3]
TFMPP Hs Full agonist 5.2 – 5.4 pKi 1,3,13
pKi 5.2 – 5.4 [1,3,13]
5-CT Hs Full agonist 5.1 – 5.5 pKi 1,3,10,13
pKi 5.1 – 5.5 [1,3,10,13]
BRL-15572 Hs Partial agonist 5.2 pKi 15
pKi 5.2 [15]
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
methylergonovine Hs Antagonist 7.0 – 7.2 pKi 1,6
pKi 7.0 – 7.2 [1,6]
1-naphthylpiperazine Hs Antagonist 6.7 – 7.0 pKi 1,3,13
pKi 6.7 – 7.0 [1,3,13]
methiothepin Hs Antagonist 6.7 – 7.0 pKi 1,3,10,13
pKi 6.7 – 7.0 [1,3,10,13]
methysergide Hs Antagonist 6.5 – 6.8 pKi 1,3,6,10,13
pKi 6.5 – 6.8 [1,3,6,10,13]
zotepine Hs Antagonist 6.5 pKi 16
pKi 6.5 [16]
sertindole Hs Antagonist 6.4 pKi 16
pKi 6.4 [16]
9-OH-risperidone Hs Antagonist 6.0 pKi 16
pKi 6.0 [16]
yohimbine Hs Antagonist 5.9 pKi 1
pKi 5.9 [1]
risperidone Hs Antagonist 5.9 pKi 16
pKi 5.9 [16]
metergoline Hs Antagonist 5.6 – 6.1 pKi 3,10,13
pKi 5.6 – 6.1 [3,10,13]
fluspirilene Hs Antagonist 5.6 pKi 16
pKi 5.6 [16]
rauwolscine Hs Antagonist 5.4 – 5.5 pKi 3,13
pKi 5.4 – 5.5 [3,13]
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:  11
Cortical areas, caudate, putamen, amygdala.
Species:  Human
Technique:  in situ hybridisation.
References:  5
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:  20
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:  10
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 [18].
Biologically Significant Variants
Type: 
Species:  Human
Description:  There have been no receptor variants reported. This suggests high evolutionary conservation of the 5-ht1e receptor.
References:  17
Available Assays
DiscoveRx PathHunter® U2OS HTR1E β-Arrestin Cell Line (Cat no. 93-0698C3) more info

REFERENCES

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 A90: 408-412. [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. Neuropharmacology33: 403-410. [PMID:7984278]

3. 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 Pharmacol484: 127-139. [PMID:14744596]

4. 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 Pharmacology123 (1): 233.

5. 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. Neuropharmacology33: 367-386. [PMID:7984275]

6. 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 Chem12: 2545-2552. [PMID:15110837]

7. 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 Chem43: 1011-1018. [PMID:10715164]

8. John GW, Pauwels PJ, Perez M, Halazy S, Le Grand B, Verscheure Y, Valentin JP, Palmier C, Wurch T, Chopin P, Marien M, Kleven MS, Koek W, Assie MB, Carilla-Durand E, Tarayre JP, Colpaert FC. (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 Ther290: 83-95. [PMID:10381763]

9. Levy FO, Holtgreve-Grez H, Tasken 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. Genomics22: 637-640. [PMID:8001977]

10. 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 A89: 5517-5521. [PMID:1608964]

11. 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 Lett136: 223-226. [PMID:1641195]

12. 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 Pharmacol368: 259-268. [PMID:10193663]

13. 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 Neurochem67: 2096-2103. [PMID:8863519]

14. Phebus LA, Johnson KW, Zgombick JM, Gilbert PJ, Van Belle K, Mancuso V, Nelson DL, Calligaro DO, Kiefer AD, Branchek TA, Flaugh ME. (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 Sci61: 2117-212. [PMID:9395253]

15. Price GW, Burton MJ, Collin LJ, Duckworth M, Gaster L, Gothert 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: 312-320. [PMID:9303567]

16. 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: 57-73. [PMID:8935801]

17. Shimron-Abarbanell D, Nothen 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 Res29: 387-390. [PMID:7609628]

18. 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 Immun14: 219-224. [PMID:10970681]

19. 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 Pharmacol125: 1413-1420. [PMID:9884068]

20. 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 Pharmacol42: 180-185. [PMID:1513320]

To cite this database page, please use the following:

Rodrigo Andrade, Nicholas M. Barnes, Gordon Baxter, Joel Bockaert, Theresa Branchek, Marlene L. Cohen, Aline Dumuis, Richard M. Eglen, Manfred Göthert, Mark Hamblin, Michel Hamon, Paul R. Hartig, René Hen, Katharine Herrick-Davis, Rebecca Hills, Daniel Hoyer, Patrick P. A. Humphrey, Klaus Peter Latté, Luc Maroteaux, Graeme R. Martin, Derek N. Middlemiss, Ewan Mylecharane, Stephen J. Peroutka, Pramod R. Saxena, Andrew Sleight, Carlos M. Villalon, Frank Yocca.
5-Hydroxytryptamine receptors: 5-ht1e receptor. Last modified on 23/11/2012. Accessed on 25/10/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=4.

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