5-Hydroxytryptamine receptor 4 is a protein that in humans is encoded by the ''HTR4'' gene.

Function

This gene is a member of the family of human

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 ...

receptors, which are G protein-coupled receptors that stimulate

cAMP Camp may refer to: Outdoor accommodation and recreation * Campsite or campground, a recreational outdoor sleeping and eating site * a temporary settlement for nomads * Camp, a term used in New England, Northern Ontario and New Brunswick to descri ...

production in response to serotonin (5-hydroxytryptamine). The gene product is a glycosylated transmembrane protein that functions in both the peripheral and central nervous system to modulate the release of various neurotransmitters. Multiple transcript variants encoding proteins with distinct C-terminal sequences have been described, but the full-length nature of some transcript variants has not been determined.

Location

The receptor is located in the alimentary tract, urinary bladder, heart and adrenal gland as well as the central nervous system (CNS). In the CNS the receptor appears in the putamen, caudate nucleus, nucleus accumbens,

globus pallidus The globus pallidus (GP), also known as paleostriatum or dorsal pallidum, is a subcortical structure of the brain. It consists of two adjacent segments, one external, known in rodents simply as the globus pallidus, and one internal, known in rod ...

, and

substantia nigra The substantia nigra (SN) is a basal ganglia structure located in the midbrain that plays an important role in reward and movement. ''Substantia nigra'' is Latin for "black substance", reflecting the fact that parts of the substantia nigra app ...

, and to a lesser extent in the

neocortex The neocortex, also called the neopallium, isocortex, or the six-layered cortex, is a set of layers of the mammalian cerebral cortex involved in higher-order brain functions such as sensory perception, cognition, generation of motor commands, sp ...

, raphe, pontine nuclei, and some areas of the thalamus. It has not been found in the cerebellum.

Isoforms

Internalization is isoform-specific.

Ligands

Several drugs that act as 5-HT₄ selective agonists have recently been introduced into use in both scientific research and clinical medicine. Some drugs that act as 5-HT₄ agonists are also active as 5-HT₃ antagonists, such as mosapride, metoclopramide, renzapride, and zacopride, and so these compounds cannot be considered highly selective. Research in this area is ongoing. Amongst these agonists prucalopride has >150-fold higher affinity for 5-HT4 receptors than for other receptors. SB-207,145 radiolabeled with carbon-11 is used as a radioligand for 5-HT₄ in

positron emission tomography Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in Metabolism, metabolic processes, and in other physiological activities including bl ...

pig and human studies.

Agonists

* BIMU-8 * Cisapride * CJ-033,466 - partial agonist * ML-10302 * Mosapride * Prucalopride * Renzapride * RS-67506 * RS-67333 - partial agonist *

SL65.0155 Capeserod (INN; development code SL65.0155) is a selective 5-HT4 receptor partial agonist with Ki = 0.6 nM and IA = 40–50% (relative to serotonin). It potently enhances cognition, learning, and memory, and also possesses antidepressant effe ...

- partial agonist * Tegaserod *

Zacopride Zacopride is a potent Antagonist (pharmacology), antagonist at the 5-HT3 receptor, 5-HT3 Receptor (biochemistry), receptor and an agonist at the 5-HT4 receptor, 5-HT4 receptor. It has anxiolytic and nootropic effects in animal models, with the (' ...

* Metoclopramide * Sulpiride * Naronapride

Antagonists

*l-lysine *

Piboserod Piboserod is a selective 5-HT4 receptor antagonist which was marketed and manufactured by GlaxoSmithKline (GSK) under the trade name Serlipet for the management of atrial fibrillation and irritable bowel syndrome. In 2007 the Norwegian compan ...

GR-113,808 GR-113808 is a drug which acts as a potent and selective 5-HT4 serotonin receptor antagonist. It is used in researching the roles of 5-HT4 receptors in various processes, and has been used to test some of the proposed therapeutic effects of sele ...

(1-methyl-1H-indole-3-carboxylic acid, -[2-[(methylsulfonyl)aminothyl">-[(methylsulfonyl)amino.html" ;"title="-[2-[(methylsulfonyl)amino">-[2-[(methylsulfonyl)aminothyl4-piperidinyl]methyl ester) * GR-125,487 * RS-39604 (1-[4-Amino-5-chloro-2-(3,5-dimethoxyphenyl)methyloxy]-3-[1-[2-methylsulphonylamino]piperidin-4-yl]propan-1-one) * SB-203,186 * SB-204,070 *([Methoxy-¹¹C]1-butylpiperidin-4-yl)methyl 4-amino-3-methoxybenzoate * Chamomile (ethanol extract)

References

External links

* * {{DEFAULTSORT:5-Ht4 Receptor Biology of bipolar disorder Serotonin receptors