5-HT5A receptor
| HTR5A | |||
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| Identifiers | |||
Gene ontology | |||
| Molecular function | |||
| Cellular component | |||
| Biological process |
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| Sources:Amigo / QuickGO | |||
Ensembl | |||||||||
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| UniProt | |||||||||
| RefSeq (mRNA) | |||||||||
| RefSeq (protein) | |||||||||
| Location (UCSC) | Chr 7: 155.07 – 155.09 Mb | Chr 5: 28.05 – 28.06 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
| View/Edit Human | View/Edit Mouse |
5-Hydroxytryptamine (serotonin) receptor 5A, also known as HTR5A, is a
Agonists and antagonists
for 5-HT receptors, as well as serotonin uptake inhibitors, present promnesic (memory-promoting) and/or anti-amnesic effects under different conditions, and 5-HT receptors are also associated with neural changes.
Function
The gene described in this record is a member of
5-hydroxytryptamine and couples to G proteins, negatively influencing cAMP levels via Gi and Go.[7] This protein has been shown to function in part through the regulation of intracellular Ca2+ mobilization.[5] The 5-HT5A receptor has been shown to be functional in a native expression system.[8]
Rodents have been shown to possess two functional 5-HT5 receptor subtypes, 5-HT5A and 5-HT5B,[9] however while humans possess a gene coding for the 5-HT5B subtype, its coding sequence is interrupted by stop codons, making the gene non-functional, and so only the 5-HT5A subtype is expressed in human brain.[10]
It also appears to serve as a presynaptic serotonin autoreceptor.[11]
Clinical significance
The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) has been implicated in a wide range of psychiatric conditions and also has vasoconstrictive and vasodilatory effects.[5]
Selective ligands
Few highly selective ligands are commercially available for the 5-HT5A receptor. When selective activation of this receptor is desired in scientific research, the non-selective serotonin receptor agonist 5-Carboxamidotryptamine can be used in conjunction with selective antagonists for its other targets (principally 5-HT1A, 5-HT1B, 5-HT1D, and 5-HT7). Research in this area is ongoing.[12][13]
Agonists
- Lisuride – partial agonist.[15]
- 5-CT – full agonist.[15]
- Methylergometrine – full agonist.[15]
- Valerenic acid – a component of valerian, has been shown to act as a 5HT5A partial agonist.[16]
- Olanzapine – an atypical antipsychotic.[17]
- Psilocin[18]
- Another ligand that has been recently disclosed is shown below, claimed be a selective 5-HT5A agonist with Ki = 124 nM.[19]
Antagonists
- ASP-5736[20][21]
- AS-2030680[20]
- AS-2674723[20]
- MS112 – selective potent antangonist.[15]
- Latrepirdine (non-selective).[22]
- Risperidone – (non-selective), moderate 206 nM affinity.
- SB-699,551
See also
- 5-HT receptor
- 5-HT1 receptor
- 5-HT2 receptor
- 5-HT3 receptor
- 5-HT4 receptor
- 5-HT6 receptor
- 5-HT7 receptor
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000157219 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000039106 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b c "Entrez Gene: HTR5A 5-hydroxytryptamine (serotonin) receptor 5A".
- S2CID 36425845.
- PMID 9865521.
- PMID 22539842.
- PMID 8450829.
- PMID 14965244.
- S2CID 543423.
- PMID 12523486.
- PMID 18023344.
- ISBN 0-9640548-1-7
- ^ PMID 35835867.
- PMID 15921820.
- ^ Roth BL, Driscol J. "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 14 August 2017.
- PMID 20126400.
- ^ US 6750221, Garcia-Ladona FJ, Szabo L, Steiner G, Hofmann HP, "Use of 5-HT5-ligands in the treatment of neurodegenerative and neuropsychiatric disturbances", published 2004-06-15
- ^ PMID 25837935.
- PMID 25108314.
- PMID 18939977.
Further reading
- Raymond JR, Mukhin YV, Gelasco A, Turner J, Collinsworth G, Gettys TW, et al. (2002). "Multiplicity of mechanisms of serotonin receptor signal transduction". Pharmacology & Therapeutics. 92 (2–3): 179–212. PMID 11916537.
- Thomas DR (September 2006). "5-ht5A receptors as a therapeutic target". Pharmacology & Therapeutics. 111 (3): 707–714. PMID 16516972.
- Rees S, den Daas I, Foord S, Goodson S, Bull D, Kilpatrick G, Lee M (December 1994). "Cloning and characterisation of the human 5-HT5A serotonin receptor". FEBS Letters. 355 (3): 242–246. S2CID 36425845.
- Schanen NC, Scherer SW, Tsui LC, Francke U (1997). "Assignment of the 5-hydroxytryptamine (serotonin) receptor 5A gene (HTR5A) to human chromosome band 7q36.1". Cytogenetics and Cell Genetics. 72 (2–3): 187–188. PMID 8978771.
- The Sanger Centre; The Washington University Genome Sequencing Cente (November 1998). "Toward a complete human genome sequence". Genome Research. 8 (11): 1097–1108. PMID 9847074.
- Francken BJ, Josson K, Lijnen P, Jurzak M, Luyten WH, Leysen JE (May 2000). "Human 5-hydroxytryptamine(5A) receptors activate coexpressed G(i) and G(o) proteins in Spodoptera frugiperda 9 cells". Molecular Pharmacology. 57 (5): 1034–1044. PMID 10779389.
- Marazziti D, Ori M, Nardini M, Rossi A, Nardi I, Cassano GB (2001). "mRNA expression of serotonin receptors of type 2C and 5A in human resting lymphocytes". Neuropsychobiology. 43 (3): 123–126. S2CID 20724896.
- Iwata N, Ozaki N, Inada T, Goldman D (March 2001). "Association of a 5-HT(5A) receptor polymorphism, Pro15Ser, to schizophrenia". Molecular Psychiatry. 6 (2): 217–219. PMID 11317225.
- Grailhe R, Grabtree GW, Hen R (April 2001). "Human 5-HT(5) receptors: the 5-HT(5A) receptor is functional but the 5-HT(5B) receptor was lost during mammalian evolution". European Journal of Pharmacology. 418 (3): 157–167. PMID 11343685.
- Noda M, Yasuda S, Okada M, Higashida H, Shimada A, Iwata N, et al. (January 2003). "Recombinant human serotonin 5A receptors stably expressed in C6 glioma cells couple to multiple signal transduction pathways". Journal of Neurochemistry. 84 (2): 222–232. S2CID 7364018.
- Khorana N, Smith C, Herrick-Davis K, Purohit A, Teitler M, Grella B, et al. (August 2003). "Binding of tetrahydrocarboline derivatives at human 5-HT5A receptors". Journal of Medicinal Chemistry. 46 (18): 3930–3937. PMID 12930153.
- Dietz BM, Mahady GB, Pauli GF, Farnsworth NR (August 2005). "Valerian extract and valerenic acid are partial agonists of the 5-HT5a receptor in vitro". Brain Research. Molecular Brain Research. 138 (2): 191–197. PMID 15921820.
External links
- "5-ht5a". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
- Human HTR5A genome location and HTR5A gene details page in the UCSC Genome Browser.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.