5-HT5A receptor

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

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. This protein has been shown to function in part through the regulation of intracellular Ca²⁺ mobilization. The 5-HT_5A receptor has been shown to be functional in a native expression system.

Rodents have been shown to possess two functional 5-HT₅ receptor subtypes, 5-HT_5A and 5-HT_5B, 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.

It also appears to serve as a presynaptic serotonin autoreceptor.

The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) has been implicated in a wide range of psychiatric conditions and also has vasoconstrictive and vasodilatory effects.

Few highly selective ligands are commercially available for the 5-HT_5A receptor, though the field has expanded considerably in recent years. 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.

• LSD:(+)-lysergic acid.
• Lisuride – partial agonist.
• 5-CT – full agonist.
• Methylergometrine – full agonist.
• Valerenic acid – a component of valerian, has been shown to act as a 5HT_5A partial agonist.
• Olanzapine – an atypical antipsychotic.
• Psilocin
• 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.

• ASP5736
• AS-2030680
• AS-2674723
• MS112 – selective potent antangonist.
• Latrepirdine (non-selective).
• Risperidone – (non-selective), moderate 206 nM affinity.
• SB-699,551

• 5-HT receptor
• 5-HT₁ receptor
• 5-HT₂ receptor
• 5-HT₃ receptor
• 5-HT₄ receptor
• 5-HT₆ receptor
• 5-HT₇ receptor

• "5-ht_5a". 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.