5-HT2B Receptor - Function

Function

The 5-HT₂ receptors (of which the 5-HT_2B receptor is a subtype) mediate many of the central and peripheral physiologic functions of serotonin. Cardiovascular effects include contraction of blood vessels and shape changes in platelets; central nervous system effects include neuronal sensitization to tactile stimuli and mediation of some of the effects of phenylisopropylamine hallucinogens.

The 5-HT_2B receptor subtype is involved in:

• CNS: presynaptic inhibition, behavioural effects
• Vascular: pulmonary vasoconstriction
• Cardiac: The 5-HT_2B receptor regulates cardiac structure and functions as demonstrated by the abnormal cardiac development observed in 5-HT_2B receptor null mice. The 5-HT_2B receptor stimulation can also lead to pathological proliferation of cardiac valves fibroblasts, which with chronic overstimulation of 5-HT_2B can lead to a severe valvulopathy. Moreover, 5-HT_2B receptors were recently shown to be overexpressed in human failing heart and antagonists of 5-HT_2B receptors were uncovered to prevent both angiotensin II or beta-adrenergic agonist-induced pathological cardiac hypertrophy in mouse.

• Serotonin transporter: 5-HT_2B receptors regulate serotonin release via the serotonin transporter, and are important both to normal physiological regulation of serotonin levels in blood plasma, and with the abnormal acute serotonin release produced by drugs such as MDMA. Surprisingly however 5-HT_2B receptor activation appears to be protective against the development of serotonin syndrome following elevated extracellular serotonin levels, despite its role in modulating serotonin release.