title: 5-hydroxytryptamine receptors in the human cardiovascular system.
abstract: The human cardiovascular system is exposed to plasma 5-hydroxytryptamine (5-HT, serotonin), usually released from platelets. 5-HT can produce harmful acute and chronic effects. The acute cardiac effects of 5-HT consist of tachycardia (preceded on occasion by a brief reflex bradycardia), increased atrial contractility and production of atrial arrhythmias. Acute inotropic, lusitropic and arrhythmic effects of 5-HT on human ventricle become conspicuous after inhibition of phosphodiesterase (PDE) activity. Human cardiostimulation is mediated through 5-HT4 receptors. Atrial and ventricular PDE3 activity exerts a protective role against potentially harmful cardiostimulation. Chronic exposure to high levels of 5-HT (from metastatic carcinoid tumours), the anorectic drug fenfluramine and its metabolites, as well as the ecstasy drug 3,4-methylenedioxymethamphetamine (MDMA) and its metabolite 3,4-methylenedioxyamphetamine (MDA) are associated with proliferative disease and thickening of cardiac valves, mediated through 5-HT2B receptors. 5-HT2B receptors have an obligatory physiological role in murine cardiac embryology but whether this happens in humans requires research. Congenital heart block (CHB) is, on occasion, associated with autoantibodies against 5-HT4 receptors. Acute vascular constriction by 5-HT is usually shared by 5-HT1B and 5-HT2A receptors, except in intracranial arteries which constrict only through 5-HT1B receptors. Both 5-HT1B and 5-HT2A receptors can mediate coronary artery spasm but only 5-HT1B receptors appear involved in coronary spasm of patients treated with triptans or with Prinzmetal angina. 5-HT2A receptors constrict the portal venous system including oesophageal collaterals in cirrhosis. Chronic exposure to 5-HT can contribute to pulmonary hypertension through activation of constrictor 5-HT1B receptors and proliferative 5-HT2B receptors, and possibly through direct intracellular effects.
authors.affiliation: Department of Physiology, University of Cambridge, UK.
authors.forename: Alberto J
authors.initials: AJ
authors.lastname: Kaumann
authors.forename: Finn Olav
authors.initials: FO
authors.lastname: Levy
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000502:physiology*; D002318:Cardiovascular Diseases / Q000209:etiology*; D006339:Heart Rate; D006801:Humans; D009154:Mutation; D009200:Myocardial Contraction; D011110:Polymorphism, Genetic; D011985:Receptors, Serotonin / Q000235:genetics / Q000502:physiology*; D012701:Serotonin / Q000502:physiology
chemical_list: D011985:Receptors, Serotonin; D012701:Serotonin