5-Hydroxytryptamine (serotonin) receptor 5A, also known as HTR5A, is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
that in humans is encoded by the ''HTR5A''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
.
Agonists
An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an ...
and
antagonist
An antagonist is a character in a story who is presented as the chief foe of the protagonist.
Etymology
The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, riv ...
s 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
Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vas ...
and couples to
G protein
G proteins, also known as guanine nucleotide-binding proteins, are a family of proteins that act as molecular switches inside cells, and are involved in transmitting signals from a variety of stimuli outside a cell to its interior. Their act ...
s, negatively influencing cAMP levels via G
i and G
o.
This protein has been shown to function in part through the regulation of intracellular Ca
2+ 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-HT
5 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.
Clinical significance
The neurotransmitter
serotonin
Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vas ...
(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-HT
5A receptor. When selective activation of this receptor is desired in scientific research, the non-selective serotonin receptor agonist
5-Carboxamidotryptamine
5-Carboxamidotryptamine (5-CT) is a tryptamine derivative closely related to the neurotransmitter serotonin.
5-CT acts as a non-selective, high-affinity full agonist at the 5-HT1A, 5-HT1B, 5-HT1D, 5-HT5A, and 5-HT7 receptors, as well as ...
can be used in conjunction with selective antagonists for its other targets (principally 5-HT
1A, 5-HT
1B, 5-HT
1D, and 5-HT
7). Research in this area is ongoing.
Agonists
*
LSD:(+)-lysergic acid,
*
Lisuride
Lisuride, sold under the brand name Dopergin among others, is a monoaminergic medication of the ergoline class which is used in the treatment of Parkinson's disease, migraine, and high prolactin levels. It is taken by mouth.
Side effects of lis ...
, partial agonist.
*
5-CT, full agonist.
*
Methylergometrine
Methylergometrine, also known as methylergonovine and sold under the brand name Methergine, is a medication of the ergoline and lysergamide groups which is used as an oxytocic in obstetrics and in the treatment of migraine. It reportedly produces ...
, full agonist.
*
Valerenic acid
Valerenic acid is a sesquiterpenoid constituent of the essential oil of the valerian plant.
Valerian is used as a herbal sedative which may be helpful in the treatment of insomnia. Valerenic acid may be at least partly responsible for valeri ...
, a component of
valerian, has been shown to act as a 5HT
5A partial agonist.
*
Olanzapine
Olanzapine (sold under the trade name Zyprexa among others) is an atypical antipsychotic primarily used to treat schizophrenia and bipolar disorder. For schizophrenia, it can be used for both new-onset disease and long-term maintenance. It is ta ...
, an
atypical antipsychotic
The atypical antipsychotics (AAP), also known as second generation antipsychotics (SGAs) and serotonin–dopamine antagonists (SDAs), are a group of antipsychotic drugs (antipsychotic drugs in general are also known as major tranquilizers and ne ...
.
*Psilocin
* Another ligand that has been recently disclosed is shown below, claimed be a selective 5-HT
5A agonist with K
i = 124 nM.
Antagonists
*
ASP-5736
* AS-2030680
* AS-2674723
* MS112, selective potent antangonist.
*
Latrepirdine
Latrepirdine (INN, also known as dimebolin and sold as Dimebon) is an antihistamine drug which has been used clinically in Russia since 1983.
Research was conducted in both Russia and western nations into potential applications as a neuroprotect ...
(non-selective)
*
Risperidone
Risperidone, sold under the brand name Risperdal among others, is an atypical antipsychotic used to treat schizophrenia and bipolar disorder. It is taken either by mouth or by injection (subcutaneous or intramuscular). The injectable versions ...
(non-selective), moderate 206 nM affinity.
*
SB-699,551
SB-699551 is a drug which was the first compound developed to act as a selective antagonist for the serotonin receptor 5-HT5A, with selectivity of around 100x over other serotonin receptor subtypes. Multiple therapeutic roles have been suggested ...
See also
*
5-HT receptor
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 neur ...
*
5-HT1 receptor
*
5-HT2 receptor
*
5-HT3 receptor
*
5-HT4 receptor
*
5-HT6 receptor
*
5-HT7 receptor
References
Further reading
*
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External links
*
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{{DEFAULTSORT:5-Ht5a Receptor
Serotonin receptors