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.

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. This protein has been shown to function in part through the regulation of intracellular Ca2+ mobilization. The 5-HT5A 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-HT5A and 5-HT5B, 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.

It also appears to serve as a presynaptic serotonin autoreceptor.

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.

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.

Agonists

 * 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 5HT5A partial agonist.
 * Olanzapine – an atypical antipsychotic.
 * Psilocin
 * Another ligand that has been recently disclosed is shown below, claimed be a selective 5-HT5A agonist with Ki = 124 nM.



Antagonists

 * ASP-5736
 * AS-2030680
 * AS-2674723
 * MS112 – selective potent antangonist.
 * Latrepirdine (non-selective).
 * Risperidone – (non-selective), moderate 206 nM affinity.
 * SB-699,551