5-HT5A receptor

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.

HTR5A
Identifiers
Aliases	HTR5A, 5-HT5A, 5-HT5A receptor, 5-hydroxytryptamine receptor 5A
External IDs	OMIM: 601305; MGI: 96283; HomoloGene: 22461; GeneCards: HTR5A; OMA:HTR5A - orthologs
Gene location (Human) Chr. Chromosome 7 (human)[1] Band 7q36.2 Start 155,070,324 bp[1] End 155,087,392 bp[1]
Gene location (Mouse) Chr. Chromosome 5 (mouse)[2] Band 5 B1|5 13.24 cM Start 28,047,147 bp[2] End 28,060,086 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in cerebellar hemisphere right hemisphere of cerebellum prefrontal cortex right frontal lobe Brodmann area 9 anterior cingulate cortex secondary oocyte Hypothalamus nucleus accumbens superior frontal gyrus Top expressed in secondary oocyte intestinal villus Ileal epithelium zygote lumbar subsegment of spinal cord choroid plexus of fourth ventricle perirhinal cortex entorhinal cortex gastrula primary visual cortex More reference expression data BioGPS More reference expression data
Gene ontology Molecular function G protein-coupled receptor activity signal transducer activity G protein-coupled serotonin receptor activity neurotransmitter receptor activity serotonin binding Cellular component integral component of membrane perikaryon plasma membrane rough endoplasmic reticulum Golgi apparatus integral component of plasma membrane membrane dendrite integral component of postsynaptic specialization membrane Biological process G protein-coupled receptor signaling pathway G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger brain development response to estradiol hippocampus development cAMP-mediated signaling signal transduction adenylate cyclase-inhibiting serotonin receptor signaling pathway chemical synaptic transmission Sources:Amigo / QuickGO
Orthologs Species Human Mouse 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
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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 G_i and G_o.^[7] This protein has been shown to function in part through the regulation of intracellular Ca²⁺ mobilization.^[5] The 5-HT_5A 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-HT_5A and 5-HT_5B,^[9] however while humans possess a gene coding for the 5-HT_5B subtype, its coding sequence is interrupted by stop codons, making the gene non-functional, and so only the 5-HT_5A 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-HT_5A receptor, though the field has expanded considerably in recent years.^[12][13] 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-HT_1A, 5-HT_1B, 5-HT_1D, and 5-HT₇). Research in this area is ongoing.^[14][15]

Agonists

• LSD:(+)-lysergic acid.^[16][17]
• Lisuride – partial agonist.^[17]
• 5-CT – full agonist.^[17]
• Methylergometrine – full agonist.^[17]
• Valerenic acid – a component of valerian, has been shown to act as a 5HT_5A partial agonist.^[18]
• Olanzapine – an atypical antipsychotic.^[19]
• Psilocin^[20]
• Aripiprazole - an atypical antipsychotic
• Mirtazapine - an atypical antidepressant
• UCSF648 - selective 5-HT_5A partial agonist
• Another ligand that has been recently disclosed is shown below, claimed be a selective 5-HT_5A agonist with K_i = 124 nM.^[21]

Antagonists

• ASP5736^[22][23]
• AS-2030680^[22]
• AS-2674723^[22]
• MS112 – selective potent antangonist.^[17]
• Latrepirdine (non-selective).^[24]
• 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