Biology:5-HT5A receptor
 Generic protein structure example |
5-Hydroxytryptamine (serotonin) receptor 5A, also known as HTR5A, is a protein that in humans is encoded by the HTR5A gene.[1][2] 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 receptor family and encodes a multi-pass membrane protein that functions as a receptor for 5-hydroxytryptamine and couples to G proteins, negatively influencing cAMP levels via Gi and Go.[3] This protein has been shown to function in part through the regulation of intracellular Ca2+ mobilization.[1] The 5-HT5A receptor has been shown to be functional in a native expression system.[4]
Rodents have been shown to possess two functional 5-HT5 receptor subtypes, 5-HT5A and 5-HT5B,[5] 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.[6]
It also appears to serve as a presynaptic serotonin autoreceptor.[7]
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.[1]
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.[8][9]
Agonists
- LSD:(+)-lysergic acid.[10][11]
- Lisuride – partial agonist.[11]
- 5-CT – full agonist.[11]
- Methylergometrine – full agonist.[11]
- Valerenic acid – a component of valerian, has been shown to act as a 5HT5A partial agonist.[12]
- Olanzapine – an atypical antipsychotic.[13]
- Psilocin[14]
- Another ligand that has been recently disclosed is shown below, claimed be a selective 5-HT5A agonist with Ki = 124 nM.[15]
Antagonists
- ASP-5736[16][17]
- AS-2030680[16]
- AS-2674723[16]
- MS112 – selective potent antangonist.[11]
- Latrepirdine (non-selective).[18]
- 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
- ↑ 1.0 1.1 1.2 "Entrez Gene: HTR5A 5-hydroxytryptamine (serotonin) receptor 5A". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3361.
- ↑ "Cloning and characterisation of the human 5-HT5A serotonin receptor". FEBS Letters 355 (3): 242–246. December 1994. doi:10.1016/0014-5793(94)01209-1. PMID 7988681.
- ↑ "The human 5-ht5A receptor couples to Gi/Go proteins and inhibits adenylate cyclase in HEK 293 cells". European Journal of Pharmacology 361 (2–3): 299–309. November 1998. doi:10.1016/S0014-2999(98)00744-4. PMID 9865521.
- ↑ "The native serotonin 5-HT(5A) receptor: electrophysiological characterization in rodent cortex and 5-HT(1A)-mediated compensatory plasticity in the knock-out mouse". The Journal of Neuroscience 32 (17): 5804–5809. April 2012. doi:10.1523/JNEUROSCI.4849-11.2012. PMID 22539842.
- ↑ "Mouse 5-hydroxytryptamine5A and 5-hydroxytryptamine5B receptors define a new family of serotonin receptors: cloning, functional expression, and chromosomal localization". Molecular Pharmacology 43 (3): 313–319. March 1993. PMID 8450829. http://molpharm.aspetjournals.org/cgi/reprint/43/3/313.
- ↑ "5-HT5 receptors". Current Drug Targets. CNS and Neurological Disorders 3 (1): 53–58. February 2004. doi:10.2174/1568007043482606. PMID 14965244.
- ↑ "SB-699551-A (3-cyclopentyl-N-[2-(dimethylamino)ethyl]-N-[(4'-{[(2-phenylethyl)amino]methyl}-4-biphenylyl)methyl]propanamide dihydrochloride), a novel 5-ht5A receptor-selective antagonist, enhances 5-HT neuronal function: Evidence for an autoreceptor role for the 5-ht5A receptor in guinea pig brain". Neuropharmacology 51 (3): 566–577. September 2006. doi:10.1016/j.neuropharm.2006.04.019. PMID 16846620.
- ↑ "In the search for selective ligands of 5-HT5, 5-HT6 and 5-HT7 serotonin receptors". Polish Journal of Pharmacology 54 (4): 327–341. 2002. PMID 12523486. http://www.if-pan.krakow.pl/pjp/pdf/2002/4_327.pdf.
- ↑ "Cyclic guanidines as dual 5-HT5A/5-HT7 receptor ligands: optimising brain penetration". Bioorganic & Medicinal Chemistry Letters 18 (1): 262–266. January 2008. doi:10.1016/j.bmcl.2007.10.078. PMID 18023344.
- ↑ The RBI Handbook of Receptor Classification and Signal Transduction, page 114 (1995)ISBN:0-9640548-1-7
- ↑ 11.0 11.1 11.2 11.3 11.4 "Inactive and active state structures template selective tools for the human 5-HT5A receptor". Nature Structural & Molecular Biology 29 (7): 677–687. July 2022. doi:10.1038/s41594-022-00796-6. PMID 35835867.
- ↑ "Valerian extract and valerenic acid are partial agonists of the 5-HT5a receptor in vitro". Brain Research. Molecular Brain Research 138 (2): 191–197. August 2005. doi:10.1016/j.molbrainres.2005.04.009. 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.
- ↑ "Psychedelics and the human receptorome". PLOS ONE 5 (2): e9019. February 2010. doi:10.1371/journal.pone.0009019. PMID 20126400. Bibcode: 2010PLoSO...5.9019R.
- ↑ Garcia-Ladona FJ, Szabo L, Steiner G, Hofmann HP, "Use of 5-HT5-ligands in the treatment of neurodegenerative and neuropsychiatric disturbances", US patent 6750221, published 2004-06-15
- ↑ 16.0 16.1 16.2 "Novel 5-HT5A receptor antagonists ameliorate scopolamine-induced working memory deficit in mice and reference memory impairment in aged rats". Journal of Pharmacological Sciences 127 (3): 362–369. March 2015. doi:10.1016/j.jphs.2015.02.006. PMID 25837935.
- ↑ "ASP5736, a novel 5-HT5A receptor antagonist, ameliorates positive symptoms and cognitive impairment in animal models of schizophrenia". European Neuropsychopharmacology 24 (10): 1698–1708. October 2014. doi:10.1016/j.euroneuro.2014.07.009. PMID 25108314.
- ↑ "Evaluation of Dimebon in cellular model of Huntington's disease". Molecular Neurodegeneration 3 (1): 15. October 2008. doi:10.1186/1750-1326-3-15. PMID 18939977.
Further reading
- "Multiplicity of mechanisms of serotonin receptor signal transduction". Pharmacology & Therapeutics 92 (2–3): 179–212. 2002. doi:10.1016/S0163-7258(01)00169-3. PMID 11916537.
- "5-ht5A receptors as a therapeutic target". Pharmacology & Therapeutics 111 (3): 707–714. September 2006. doi:10.1016/j.pharmthera.2005.12.006. PMID 16516972.
- "Cloning and characterisation of the human 5-HT5A serotonin receptor". FEBS Letters 355 (3): 242–246. December 1994. doi:10.1016/0014-5793(94)01209-1. PMID 7988681.
- "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. 1997. doi:10.1159/000134184. 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. doi:10.1101/gr.8.11.1097. PMID 9847074.
- "Human 5-hydroxytryptamine(5A) receptors activate coexpressed G(i) and G(o) proteins in Spodoptera frugiperda 9 cells". Molecular Pharmacology 57 (5): 1034–1044. May 2000. PMID 10779389.
- "mRNA expression of serotonin receptors of type 2C and 5A in human resting lymphocytes". Neuropsychobiology 43 (3): 123–126. 2001. doi:10.1159/000054878. PMID 11287788.
- "Association of a 5-HT(5A) receptor polymorphism, Pro15Ser, to schizophrenia". Molecular Psychiatry 6 (2): 217–219. March 2001. doi:10.1038/sj.mp.4000829. PMID 11317225.
- "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. April 2001. doi:10.1016/S0014-2999(01)00933-5. PMID 11343685.
- "Recombinant human serotonin 5A receptors stably expressed in C6 glioma cells couple to multiple signal transduction pathways". Journal of Neurochemistry 84 (2): 222–232. January 2003. doi:10.1046/j.1471-4159.2003.01518.x. PMID 12558985.
- "Binding of tetrahydrocarboline derivatives at human 5-HT5A receptors". Journal of Medicinal Chemistry 46 (18): 3930–3937. August 2003. doi:10.1021/jm030080s. PMID 12930153.
- "Valerian extract and valerenic acid are partial agonists of the 5-HT5a receptor in vitro". Brain Research. Molecular Brain Research 138 (2): 191–197. August 2005. doi:10.1016/j.molbrainres.2005.04.009. PMID 15921820.
External links
- "5-ht5a". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2331.
- 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.
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