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Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
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5-HT receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on 5-HT receptors [65] and subsequently revised [59]) are, with the exception of the ionotropic 5-HT3 class, GPCRs where the endogenous agonist is 5-hydroxytryptamine. The diversity of metabotropic 5-HT receptors is increased by alternative splicing that produces isoforms of the 5-HT2A (non-functional), 5-HT2C (non-functional), 5-HT4, 5-HT6 (non-functional) and 5-HT7 receptors. Unique amongst the GPCRs, RNA editing produces 5-HT2C receptor isoforms that differ in function, such as efficiency and specificity of coupling to Gq/11 and also pharmacology [14,159]. Most 5-HT receptors (except 5-ht1e and 5-ht5b) play specific roles mediating functional responses in different tissues (reviewed by [125,150]).
5-HT1A receptor C Show summary »« Hide summary More detailed page
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* Key recommended reading is highlighted with an asterisk
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Subcommittee members:
Nicholas M. Barnes (Chairperson)
Daniel Hoyer (Co-chairperson)
Rodrigo Andrade
Joel Bockaert
Amy Butler
Michel Hamon
Julie Hensler
Katharine Herrick-Davis
Luc Maroteaux
Graeme R. Martin
John Neumaier (Past chairperson)
John A. Peters
Bryan Roth
Trevor Sharp
Carlos M. Villalon |
Other contributors:
Gordon Baxter
Theresa Branchek
Marlene L. Cohen
Aline Dumuis
Richard M. Eglen
Manfred Göthert
Mark Hamblin
Paul R. Hartig
René Hen
Rebecca Hills
Patrick P. A. Humphrey
Klaus Peter Latté
Derek N. Middlemiss
Ewan Mylecharane
Stephen J. Peroutka
Pramod R. Saxena
Andrew Sleight
Frank Yocca |
Database page citation (select format):
Concise Guide to PHARMACOLOGY citation:
Alexander SPH, Christopoulos A, Davenport AP, Kelly E, Mathie AA, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: G protein-coupled receptors. Br J Pharmacol. 180 Suppl 2:S23-S144.
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Tabulated pKi and KD values refer to binding to human 5-HT receptors unless indicated otherwise. The nomenclature of 5-HT1B/5-HT1D receptors has been revised [59]. Only the non-rodent form of the receptor was previously called 5-HT1D: the human 5-HT1B receptor (tabulated) displays a different pharmacology to the rodent forms of the receptor due to Thr335 of the human sequence being replaced by Asn in rodent receptors [57]. Wang et al. (2013) report X-ray structures which reveal the binding modality of ergotamine and dihydroergotamine (DHE) to the 5-HT1B receptor in comparison with the structure of the 5-HT2B receptor [156]; some of these drugs adopt rather different conformations depending on the target receptor [123]. Various 5-HT receptors have multiple partners in addition to G proteins, which may affect function and pharmacology [95]. NAS181 is a selective antagonist of the rodent 5-HT1B receptor. Fananserin (LSD) and ketanserin bind with high affinity to dopamine D4 and histamine H1 receptors respectively, and ketanserin is a potent α1 adrenoceptor antagonist, in addition to blocking 5-HT2A receptors. Lysergic acid (LSD) and ergotamine show a strong preference for arrestin recruitment over G protein coupling at the 5-HT2B receptor, with no such preference evident at 5-HT1B receptors, and they also antagonise 5-HT7A receptors [151]. DHE (dihydroergocryptine), pergolide and cabergoline also show significant preference for arrestin recruitment over G protein coupling at 5-HT2B receptors [151]. The 5-HT2B (and other 5-HT) receptors interact with immunocompetent cells [118]. The serotonin antagonist mesulergine was key to the discovery of the 5-HT2C receptor [122], initially known as 5-HT1C [4]. The human 5-HT5A receptor may couple to several signal transduction pathways when stably expressed in C6 glioma cells [116] and rodent prefrontal cortex (layer V pyramidal neurons) [51]. The human orthologue of the mouse 5-ht5b receptor is non-functional (stop codons); the 5-ht1e receptor has not been cloned from mouse, or rat, impeding definition of its function [57]. In addition to accepted receptors, an 'orphan' receptor, unofficially termed 5-HT1P, has been described [47].