5-HT5A receptor
5-Hydroxytryptamine 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 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 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, 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. 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
- Aripiprazole - an atypical antipsychotic
- Mirtazapine - an atypical antidepressant
- UCSF648 - selective 5-HT5A partial agonist
- Another ligand that has been recently disclosed is shown below, claimed be a selective 5-HT5A agonist with Ki = 124 nM.
Antagonists
- ASP5736
- AS-2030680
- AS-2674723
- MS112 selective potent antangonist.
- Latrepirdine.
- Risperidone, moderate 206 nM affinity.
- SB-699,551