5-Hydroxytryptamine receptor 4 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, respon ...

that in humans is encoded by the ''HTR4''

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 b ...

Function

This gene is a member of the family of human serotonin receptors, which are

G protein-coupled receptors G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related p ...

that stimulate cAMP 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 A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neuro ...

. 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 The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans an ...

urinary bladder The urinary bladder, or simply bladder, is a hollow organ in humans and other vertebrates that stores urine from the kidneys before disposal by urination. In humans the bladder is a distensible organ that sits on the pelvic floor. Urine enters ...

heart The heart is a muscular organ found in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as carbon diox ...

and

adrenal gland The adrenal glands (also known as suprarenal glands) are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. They are found above the kidneys. Each gland has an outer cortex w ...

as well as the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...

(CNS). In the CNS the receptor appears in the putamen, caudate nucleus,

nucleus accumbens The nucleus accumbens (NAc or NAcc; also known as the accumbens nucleus, or formerly as the ''nucleus accumbens septi'', Latin for "nucleus adjacent to the septum") is a region in the basal forebrain rostral to the preoptic area of the hypot ...

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 rode ...

, 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 a ...

, 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, ...

raphe Raphe (; from Greek ῥαφή, "seam"Liddell, H.G. & Scott, R. (1940). ''A Greek-English Lexicon. revised and augmented throughout by Sir Henry Stuart Jones. with the assistance of. Roderick McKenzie.'' Oxford: Clarendon Press.) has several diffe ...

, pontine nuclei, and some areas of the

thalamus The thalamus (from Greek θάλαμος, "chamber") is a large mass of gray matter located in the dorsal part of the diencephalon (a division of the forebrain). Nerve fibers project out of the thalamus to the cerebral cortex in all direction ...

. 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 Carbon (6C) has 15 known isotopes, from to , of which and are stable. The longest-lived radioisotope is , with a half-life of years. This is also the only carbon radioisotope found in nature—trace quantities are formed cosmogenically by ...

is used as a

radioligand A radioligand is a radioactive biochemical substance (in particular, a ligand that is radiolabeled) that is used for diagnosis or for research-oriented study of the receptor systems of the body. In a neuroimaging application the radioligand is ...

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 metabolic processes, and in other physiological activities including blood flow, ...

pig and human studies.

Agonists

* BIMU-8 *

Cisapride Cisapride is a gastroprokinetic agent, a drug that increases motility in the upper gastrointestinal tract. It acts directly as a serotonin 5-HT4 receptor agonist and indirectly as a parasympathomimetic. Stimulation of the serotonin receptors i ...

* CJ-033,466 - partial agonist * ML-10302 *

Mosapride Mosapride is a gastroprokinetic agent that acts as a selective 5HT4 agonist. The major active metabolite of mosapride, known as M1, additionally acts as a 5HT3 antagonist, which accelerates gastric emptying throughout the whole of the gastro ...

* Prucalopride * Renzapride * RS-67506 *

RS-67333 RS-67,333 is a drug which has been investigated as a potential rapid-acting antidepressant, nootropic, and treatment for Alzheimer's disease. It is a high-affinity 5-HT4 receptor 5-Hydroxytryptamine receptor 4 is a protein that in humans is ...

- 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 *

Metoclopramide Metoclopramide is a medication used for stomach and esophageal problems. It is commonly used to treat and prevent nausea and vomiting, to help with emptying of the stomach in people with delayed stomach emptying, and to help with gastroesoph ...

* 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