5-HT5A receptor

Last updated
HTR5A
Identifiers
Aliases HTR5A , 5-HT5A, 5-HT5A receptor, 5-hydroxytryptamine receptor 5A
External IDs OMIM: 601305 MGI: 96283 HomoloGene: 22461 GeneCards: HTR5A
Orthologs
SpeciesHumanMouse
Entrez

3361

15563

Ensembl

ENSG00000157219

ENSMUSG00000039106

UniProt

P47898

P30966

RefSeq (mRNA)

NM_024012

NM_008314

RefSeq (protein)

NP_076917

NP_032340

Location (UCSC) Chr 7: 155.07 – 155.09 Mb Chr 5: 28.05 – 28.06 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

5-Hydroxytryptamine (serotonin) receptor 5A, also known as HTR5A, is a protein that in humans is encoded by the HTR5A gene. [5] [6] 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.

Contents

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. [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

DE19900637A1 5HT5A ligand.png

Antagonists

See also

Related Research Articles

<span class="mw-page-title-main">5-HT receptor</span> Class of transmembrane proteins

5-HT receptors, 5-hydroxytryptamine receptors, or serotonin receptors, are a group of G protein-coupled receptor and ligand-gated ion channels found in the central and peripheral nervous systems. They mediate both excitatory and inhibitory neurotransmission. The serotonin receptors are activated by the neurotransmitter serotonin, which acts as their natural ligand.

5-HT<sub>2A</sub> receptor Subtype of serotonin receptor

The 5-HT2A receptor is a subtype of the 5-HT2 receptor that belongs to the serotonin receptor family and is a G protein-coupled receptor (GPCR). The 5-HT2A receptor is a cell surface receptor, but has several intracellular locations.

<span class="mw-page-title-main">Serotonin receptor agonist</span> Neurotransmission-modulating substance

A serotonin receptor agonist is an agonist of one or more serotonin receptors. They activate serotonin receptors in a manner similar to that of serotonin, a neurotransmitter and hormone and the endogenous ligand of the serotonin receptors.

The 5-HT3 receptor belongs to the Cys-loop superfamily of ligand-gated ion channels (LGICs) and therefore differs structurally and functionally from all other 5-HT receptors (5-hydroxytryptamine, or serotonin receptors) which are G protein-coupled receptors. This ion channel is cation-selective and mediates neuronal depolarization and excitation within the central and peripheral nervous systems.

<span class="mw-page-title-main">5-Methoxytryptamine</span> Chemical compound

5-Methoxytryptamine (5-MT), also known as mexamine, is a tryptamine derivative closely related to the neurotransmitters serotonin and melatonin. 5-MT has been shown to occur naturally in the body in low levels. It is biosynthesized via the deacetylation of melatonin in the pineal gland.

5-HT<sub>2C</sub> receptor Serotonin receptor protein distributed mainly in the choroid plexus

The 5-HT2C receptor is a subtype of 5-HT2 receptor that binds the endogenous neurotransmitter serotonin (5-hydroxytryptamine, 5-HT). Like all 5-HT2 receptors, it is a G protein-coupled receptor (GPCR) that is coupled to Gq/G11 and mediates excitatory neurotransmission. HTR2C denotes the human gene encoding for the receptor, that in humans is located at the X chromosome. As males have one copy of the gene and in females one of the two copies of the gene is repressed, polymorphisms at this receptor can affect the two sexes to differing extent.

5-HT<sub>4</sub> receptor Protein-coding gene in the species Homo sapiens

5-Hydroxytryptamine receptor 4 is a protein that in humans is encoded by the HTR4 gene.

5-HT<sub>1A</sub> receptor Serotonin receptor protein distributed in the cerebrum and raphe nucleus

The serotonin 1A receptor is a subtype of serotonin receptors, or 5-HT receptors, that binds serotonin, also known as 5-HT, a neurotransmitter. 5-HT1A is expressed in the brain, spleen, and neonatal kidney. It is a G protein-coupled receptor (GPCR), coupled to the Gi protein, and its activation in the brain mediates hyperpolarization and reduction of firing rate of the postsynaptic neuron. In humans, the serotonin 1A receptor is encoded by the HTR1A gene.

5-HT<sub>1B</sub> receptor Mammalian protein found in Homo sapiens

5-hydroxytryptamine receptor 1B also known as the 5-HT1B receptor is a protein that in humans is encoded by the HTR1B gene. The 5-HT1B receptor is a 5-HT receptor subtype.

5-HT<sub>1D</sub> receptor Serotonin receptor which affects locomotion and anxiety in humans

5-hydroxytryptamine (serotonin) receptor 1D, also known as HTR1D, is a 5-HT receptor, but also denotes the human gene encoding it. 5-HT1D acts on the central nervous system, and affects locomotion and anxiety. It also induces vasoconstriction in the brain.

<span class="mw-page-title-main">8-OH-DPAT</span> Chemical compound

8-OH-DPAT is a research chemical of the aminotetralin chemical class which was developed in the 1980s and has been widely used to study the function of the 5-HT1A receptor. It was one of the first major 5-HT1A receptor full agonists to be discovered.

5-HT<sub>1E</sub> receptor Protein-coding gene in the species Homo sapiens

5-hydroxytryptamine (serotonin) 1E receptor (5-HT1E) is a highly expressed human G-protein coupled receptor that belongs to the 5-HT1 receptor family. The human gene is denoted as HTR1E.

5-HT<sub>1F</sub> receptor Protein-coding gene in the species Homo sapiens

5-hydroxytryptamine (serotonin) receptor 1F, also known as HTR1F is a 5-HT1 receptor protein and also denotes the human gene encoding it.

5-HT<sub>2B</sub> receptor Mammalian protein found in Homo sapiens

5-Hydroxytryptamine receptor 2B (5-HT2B) also known as serotonin receptor 2B is a protein that in humans is encoded by the HTR2B gene. 5-HT2B is a member of the 5-HT2 receptor family that binds the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT). Like all 5-HT2 receptors, the 5-HT2A receptor is Gq/G11-protein coupled, leading to downstream activation of phospholipase C.

5-HT<sub>6</sub> receptor Protein-coding gene in the species Homo sapiens

The 5HT6 receptor is a subtype of 5HT receptor that binds the endogenous neurotransmitter serotonin (5-hydroxytryptamine, 5HT). It is a G protein-coupled receptor (GPCR) that is coupled to Gs and mediates excitatory neurotransmission. HTR6 denotes the human gene encoding for the receptor.

5-HT<sub>7</sub> receptor Protein-coding gene in the species Homo sapiens

The 5-HT7 receptor is a member of the GPCR superfamily of cell surface receptors and is activated by the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) The 5-HT7 receptor is coupled to Gs (stimulates the production of the intracellular signaling molecule cAMP) and is expressed in a variety of human tissues, particularly in the brain, the gastrointestinal tract, and in various blood vessels. This receptor has been a drug development target for the treatment of several clinical disorders. The 5-HT7 receptor is encoded by the HTR7 gene, which in humans is transcribed into 3 different splice variants.

<span class="mw-page-title-main">5-Carboxamidotryptamine</span> Chemical compound

5-Carboxamidotryptamine (5-CT) is a tryptamine derivative closely related to the neurotransmitter serotonin.

<span class="mw-page-title-main">Naphthylpiperazine</span> Chemical compound

1-(1-Naphthyl)piperazine (1-NP) is a drug which is a phenylpiperazine derivative. It acts as a non-selective, mixed serotonergic agent, exerting partial agonism at the 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, and 5-HT1F receptors, while antagonizing the 5-HT2A, 5-HT2B, and 5-HT2C receptors. It has also been shown to possess high affinity for the 5-HT3, 5-HT5A, 5-HT6, and 5-HT7 receptors, and may bind to 5-HT4 and the SERT as well. In animals it produces effects including hyperphagia, hyperactivity, and anxiolysis, of which are all likely mediated predominantly or fully by blockade of the 5-HT2C receptor.

<span class="mw-page-title-main">LY-215,840</span> Chemical compound

LY-215,840 is an ergoline derivative drug developed by Eli Lilly, which acts as a potent and selective antagonist at the serotonin 5-HT2 and 5-HT7 receptors. It has anti-hypertensive and muscle relaxant effects in animal studies.

<span class="mw-page-title-main">25CN-NBOH</span> Chemical compound

25CN-NBOH is a compound indirectly derived from the phenethylamine series of hallucinogens, which was discovered in 2014 at the University of Copenhagen. This compound is notable as one of the most selective agonist ligands for the 5-HT2A receptor yet discovered, with a pKi of 8.88 at the human 5-HT2A receptor and with 100x selectivity for 5-HT2A over 5-HT2C, and 46x selectivity for 5-HT2A over 5-HT2B. A tritiated version of 25CN-NBOH has also been accessed and used for more detailed investigations of the binding to 5-HT2 receptors and autoradiography.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000157219 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000039106 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 1 2 3 "Entrez Gene: HTR5A 5-hydroxytryptamine (serotonin) receptor 5A".
  6. ↑ 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. doi: 10.1016/0014-5793(94)01209-1 . PMID   7988681. S2CID   36425845.
  7. ↑ Francken BJ, Jurzak M, Vanhauwe JF, Luyten WH, Leysen JE (November 1998). "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. doi:10.1016/S0014-2999(98)00744-4. PMID   9865521.
  8. ↑ Goodfellow NM, Bailey CD, Lambe EK (April 2012). "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. doi:10.1523/JNEUROSCI.4849-11.2012. PMC   4644074 . PMID   22539842.
  9. ↑ Matthes H, Boschert U, Amlaiky N, Grailhe R, Plassat JL, Muscatelli F, et al. (March 1993). "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. PMID   8450829.
  10. ↑ Nelson DL (February 2004). "5-HT5 receptors". Current Drug Targets. CNS and Neurological Disorders. 3 (1): 53–58. doi:10.2174/1568007043482606. PMID   14965244.
  11. ↑ Thomas DR, Soffin EM, Roberts C, Kew JN, de la Flor RM, Dawson LA, et al. (September 2006). "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. doi:10.1016/j.neuropharm.2006.04.019. PMID   16846620. S2CID   543423.
  12. ↑ Wesołowska A (2002). "In the search for selective ligands of 5-HT5, 5-HT6 and 5-HT7 serotonin receptors" (PDF). Polish Journal of Pharmacology. 54 (4): 327–341. PMID   12523486.
  13. ↑ Peters JU, Lübbers T, Alanine A, Kolczewski S, Blasco F, Steward L (January 2008). "Cyclic guanidines as dual 5-HT5A/5-HT7 receptor ligands: optimising brain penetration". Bioorganic & Medicinal Chemistry Letters. 18 (1): 262–266. doi:10.1016/j.bmcl.2007.10.078. PMID   18023344.
  14. ↑ The RBI Handbook of Receptor Classification and Signal Transduction, page 114 (1995) ISBN   0-9640548-1-7
  15. 1 2 3 4 5 Zhang S, Chen H, Zhang C, Yang Y, Popov P, Liu J, et al. (July 2022). "Inactive and active state structures template selective tools for the human 5-HT5A receptor". Nature Structural & Molecular Biology. 29 (7): 677–687. doi:10.1038/s41594-022-00796-6. PMC   9299520 . PMID   35835867.
  16. ↑ 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. doi:10.1016/j.molbrainres.2005.04.009. PMC   5805132 . PMID   15921820.
  17. ↑ 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.
  18. ↑ Ray TS (February 2010). "Psychedelics and the human receptorome". PLOS ONE. 5 (2): e9019. Bibcode:2010PLoSO...5.9019R. doi: 10.1371/journal.pone.0009019 . PMC   2814854 . PMID   20126400.
  19. ↑ 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
  20. 1 2 3 Yamazaki M, Okabe M, Yamamoto N, Yarimizu J, Harada K (March 2015). "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. doi: 10.1016/j.jphs.2015.02.006 . PMID   25837935.
  21. ↑ Yamazaki M, Harada K, Yamamoto N, Yarimizu J, Okabe M, Shimada T, et al. (October 2014). "ASP5736, a novel 5-HT5A receptor antagonist, ameliorates positive symptoms and cognitive impairment in animal models of schizophrenia". European Neuropsychopharmacology. 24 (10): 1698–1708. doi: 10.1016/j.euroneuro.2014.07.009 . PMID   25108314.
  22. ↑ Wu J, Li Q, Bezprozvanny I (October 2008). "Evaluation of Dimebon in cellular model of Huntington's disease". Molecular Neurodegeneration. 3 (1): 15. doi: 10.1186/1750-1326-3-15 . PMC   2577671 . PMID   18939977.

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