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5-ht1e receptor

Family: 5-Hydroxytryptamine receptors

Contents:
Gene and Protein Information
Previous and Unofficial Names
Database Links
Agonists
Antagonists
Transduction Mechanisms
Tissue Distribution
Functional Assays
Gene Expression and Pathophysiology
Biologically Significant Variants
References
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 10618 (Hs)
DrugBank Target 528 (Hs)
Ensembl ENSG00000168830 (Hs)
Entrez Gene 3354 (Hs)
GeneCards HTR1E (Hs)
HomoloGene 55491 (Hs)
Human Protein Reference Database 01635 (Hs)
InterPro P28566 (Hs)
KEGG Gene hsa:3354 (Hs)
OMIM 182132 (Hs)
PharmGKB Gene PA29552 (Hs)
PhosphoSitePlus P28566 (Hs)
Protein Ontology (PRO) PRO:000001164 (Hs)
RefSeq Nucleotide NM_000865 (Hs)
RefSeq Protein NP_000856 (Hs)
TreeFam ENSG00000168830 (Hs)
UniGene Hs. 1611 (Hs)
UniProt P28566 (Hs)
Wikipedia 5-ht1e receptor
5-Hydroxytryptamine receptors
Search for 3D structures on the PDB
Search by keyword: 5-Hydroxytryptamine receptors 5-ht1e receptor Search by accession number: P28566
Natural/Endogenous Ligand(s)
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
BRL-54443 Hs Full agonist 8.7 pKi 4
5-HT Hs Full agonist 8.0 – 8.2 pKi 1,3,6,10
asenapine Hs Full agonist 8.0 pKi 16
naratriptan Hs Full agonist 7.7 pKi 12
zolmitriptan Hs Full agonist 7.7 pKi 12
lysergol Hs Full agonist 7.4 pKi 13
ergonovine Hs Full agonist 7.3 pKi 3
eletriptan Hs Full agonist 7.2 pKi 12
α-methyl-5-HT Hs Full agonist 6.9 – 7.0 pKi 1,3
rizatriptan Hs Full agonist 6.8 pKi 12
clozapine Hs Full agonist 6.4 pKi 16
ziprasidone Hs Full agonist 6.4 pKi 16
5-fluorotryptamine Hs Full agonist 6.3 pKi 3
EMDT Hs Full agonist 6.3 pKi 7
ergotamine Hs Full agonist 6.2 – 6.3 pKi 1,10
5-MeO-DMT Hs Full agonist 6.1 – 6.3 pKi 1,6
2-methyl-5-HT Hs Full agonist 6.1 pKi 1
tryptamine Hs Full agonist 5.6 – 6.5 pKi 1,3,6
donitriptan Hs Full agonist 5.9 pKi 8
quetiapine Hs Full agonist 5.9 pKi 16
5-MeOT Hs Full agonist 5.5 – 6.2 pKi 1,3,6,13
LY344864 Hs Full agonist 5.8 pKi 14
olanzapine Hs Full agonist 5.7 pKi 16
sumatriptan Hs Full agonist 5.6 – 5.8 pKi 1,3,10,12-13
DOI Hs Full agonist 5.5 – 5.8 pKi 1,3
dihydroergotamine Hs Full agonist 5.6 pKi 13
xanomeline Hs Full agonist 5.6 pKi 19
8-OH-DPAT Hs Full agonist 5.5 pKi 1,3
GR-127935 Hs Partial agonist 5.4 pKi 15
m-CPP Hs Partial agonist 5.4 pKi 3
5-CT Hs Full agonist 5.1 – 5.5 pKi 1,3,10,13
TFMPP Hs Full agonist 5.2 – 5.4 pKi 1,3,13
BRL-15572 Hs Partial agonist 5.2 pKi 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
1-naphthylpiperazine Hs Antagonist 6.7 – 7.0 pKi 1,3,13
methiothepin Hs Antagonist 6.7 – 7.0 pKi 1,3,10,13
methysergide Hs Antagonist 6.5 – 6.8 pKi 1,3,6,10,13
zotepine Hs Antagonist 6.5 pKi 16
sertindole Hs Antagonist 6.4 pKi 16
9-OH-risperidone Hs Antagonist 6.0 pKi 16
risperidone Hs Antagonist 5.9 pKi 16
yohimbine Hs Antagonist 5.9 pKi 1
metergoline Hs Antagonist 5.6 – 6.1 pKi 3,10,13
fluspirilene Hs Antagonist 5.6 pKi 16
rauwolscine Hs Antagonist 5.4 – 5.5 pKi 3,13

Explore drug-target interactions for this set of compounds using iPHACE

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
There have been no receptor variants reported. This suggests high evolutionary conservation of the 5-ht1e receptor.
Type: 
Species:  Human
References:  17

REFERENCES

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1. Adham, N., Kao, H. T., Schecter, L. E., Bard, J., Olsen, M., Urquhart, D., Durkin, M., Hartig, P. R., Weinshank, R. L. and Branchek, T. A. (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: 408-412. [PMID:8380639]

2. Adham, N., Vaysse, P. J., Weinshank, R. L. and Branchek, T. A. (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: 403-410. [PMID:7984278]

3. Bai, F., Yin, T., Johnstone, E. M., Su, C., Varga, G., Little, S. P. and Nelson, D. L. (2004) Molecular cloning and pharmacological characterization of the guinea pig 5-HT1E receptor. Eur J Pharmacol, 484: 127-139. [PMID:14744596]

4. Brown, A.M., Avenell, K., Young, T.J., Ho, M., Porter, R.A., Vimal, M and Middlemiss, D.N. (1998) BRL 54443, a potent agonist with selectivity for human cloned 5-HT1E and 5-HT1F receptors. British Journal of Pharmacology, 123 (1): 233.

5. Bruinvels, A. T., Landwehrmeyer, B., Gustafson, E. L., Durkin, M. M., Mengod, G., Branchek, T. A., Hoyer, D. and Palacios, J. M. (1994) Localization of 5-HT1B, 5-HT1D alpha, 5-HT1E and 5-HT1F receptor messenger RNA in rodent and primate brain. Neuropharmacology, 33: 367-386. [PMID:7984275]

6. Dukat, M., Smith, C., Herrick-Davis, K., Teitler, M. and Glennon, R. A. (2004) Binding of tryptamine analogs at h5-HT1E receptors: a structure-affinity investigation. Bioorg Med Chem, 12: 2545-2552. [PMID:15110837]

7. Glennon, R. A., Lee, M., Rangisetty, J. B., Dukat, M., Roth, B. L., Savage, J. E., McBride, A., Rauser, L., Hufeisen, S. and Lee, D. K. (2000) 2-Substituted tryptamines: agents with selectivity for 5-HT(6) serotonin receptors. J Med Chem, 43: 1011-1018. [PMID:10715164]

8. John, G. W., Pauwels, P. J., Perez, M., Halazy, S., Le Grand, B., Verscheure, Y., Valentin, J. P., Palmier, C., Wurch, T., Chopin, P., Marien, M., Kleven, M. S., Koek, W., Assie, M. B., Carilla-Durand, E., Tarayre, J. P. and Colpaert, F. C. (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: 83-95. [PMID:10381763]

9. Levy, F. O., Holtgreve-Grez, H., Tasken, K., Solberg, R., Ried, T. and Gudermann, T. (1994) Assignment of the gene encoding the 5-HT1E serotonin receptor (S31) (locus HTR1E) to human chromosome 6q14-q15. Genomics, 22: 637-640. [PMID:8001977]

10. McAllister, G., Charlesworth, A., Snodin, C., Beer, M. S., Noble, A. J., Middlemiss, D. N., Iversen, L. L. and 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: 5517-5521. [PMID:1608964]

11. Miller, K. J. and 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: 223-226. [PMID:1641195]

12. Napier, C., Stewart, M., Melrose, H., Hopkins, B., McHarg, A. and 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: 259-268. [PMID:10193663]

13. Parker, E. M., Izzarelli, D. G., Lewis-Higgins, L., Palmer, D. and Shapiro, R. A. (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: 2096-2103. [PMID:8863519]

14. Phebus, L. A., Johnson, K. W., Zgombick, J. M., Gilbert, P. J., Van Belle, K., Mancuso, V., Nelson, D. L., Calligaro, D. O., Kiefer, A. D., Branchek, T. A. and Flaugh, M. E. (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: 2117-212. [PMID:9395253]

15. Price, G. W., Burton, M. J., Collin, L. J., Duckworth, M., Gaster, L., Gothert, M., Jones, B. J., Roberts, C., Watson, J. M. and Middlemiss, D. N. (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, P. F., Gommeren, W., Luyten, W. H., Van Gompel, P., Lesage, A. S., De Loore, K. and Leysen, J. E. (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, M. M., Erdmann, J. and 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: 387-390. [PMID:7609628]

18. Stefulj, J., Jernej, B., Cicin-Sain, L., Rinner, I. and Schauenstein, K. (2000) mRNA expression of serotonin receptors in cells of the immune tissues of the rat. Brain Behav Immun, 14: 219-224. [PMID:10970681]

19. Watson, J., Brough, S., Coldwell, M. C., Gager, T., Ho, M., Hunter, A. J., Jerman, J., Middlemiss, D. N., Riley, G. J. and Brown, A. M. (1998) Functional effects of the muscarinic receptor agonist, xanomeline, at 5-HT1 and 5-HT2 receptors. Br J Pharmacol, 125: 1413-1420. [PMID:9884068]

20. Zgombick, J. M., Schechter, L. E., Macchi, M., Hartig, P. R., Branchek, T. A. and Weinshank, R. L. (1992) Human gene S31 encodes the pharmacologically defined serotonin 5-hydroxytryptamine1E receptor. Mol Pharmacol, 42: 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 20/05/2013. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=4.


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