HTR2B

Description

The HTR2B (5-hydroxytryptamine receptor 2B) is a protein-coding gene located on chromosome 2.

The HTR2B gene, also known as the serotonin receptor 2B gene, encodes the 5-HT2B receptor, a member of the 5-HT2 receptor family. This receptor binds serotonin (5-hydroxytryptamine) and is a Gq/G11-protein coupled receptor, activating downstream phospholipase C. While initially discovered in rat stomachs, its characterization was challenging due to its structural similarity to other 5-HT2 receptors, particularly 5-HT2C. The 5-HT2 receptors mediate numerous central and peripheral functions of serotonin, including cardiovascular effects like blood vessel contraction and platelet shape changes, and central nervous system (CNS) effects like neuronal sensitization to tactile stimuli and mediating some effects of hallucinogenic substituted amphetamines. The 5-HT2B receptor is expressed in various CNS regions, including the hypothalamus, frontal cortex, medial amygdala, and meninges. However, its primary role is in the peripheral nervous system (PNS), where it maintains the viability and efficiency of cardiac valve leaflets. The 5-HT2B receptor plays roles in various processes:

CNS: Inhibition of serotonin and dopamine uptake, influencing behavior
Vascular: Pulmonary vasoconstriction
Cardiac: Regulates cardiac structure and functions, with disruptions in 5-HT2B receptor activity leading to abnormal cardiac development in mice. Excessive stimulation causes pathological proliferation of cardiac valve fibroblasts, and chronic overstimulation results in valvulopathy. These receptors are overexpressed in failing human hearts, and antagonists of 5-HT2B receptors have been shown to prevent angiotensin II or beta-adrenergic agonist-induced pathological cardiac hypertrophy in mice.
Serotonin Transporter: 5-HT2B receptors regulate serotonin release via the serotonin transporter, essential for both normal physiological regulation of serotonin levels in blood plasma and the abnormal acute serotonin release triggered by drugs like MDMA. Interestingly, despite its role in modulating serotonin release, 5-HT2B receptor activation appears to protect against the development of serotonin syndrome following elevated extracellular serotonin levels.

The HTR2B gene encodes a G protein-coupled receptor for serotonin (5-hydroxytryptamine). It also acts as a receptor for various ergot alkaloid derivatives and psychoactive substances. Ligand binding triggers signaling through G proteins, modulating downstream effectors. Beta-arrestins inhibit G protein signaling and activate alternative signaling pathways. This signaling activates a phosphatidylinositol-calcium second messenger system, modulating phosphatidylinositol 3-kinase activity and promoting calcium release from intracellular stores. HTR2B plays a role in regulating dopamine and serotonin release and uptake, influencing neural activity. It may also be involved in pain perception and regulating behavior, including impulsive behavior. HTR2B is essential for normal embryonic cardiac myocyte proliferation and heart development, protecting cardiomyocytes against apoptosis. It participates in the adaptation of pulmonary arteries to chronic hypoxia and vasoconstriction. HTR2B is also crucial for normal osteoblast function, proliferation, and maintaining bone density. It is required for the normal proliferation of interstitial cells of Cajal in the intestine. HTR2B interacts with MPDZ via its C-terminus.

HTR2B is also known as 5-HT(2B), 5-HT-2B, 5-HT2B.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing