title: Endothelins -- clinical perspectives.
abstract: Endothelins (ET) are a group of endogenous peptides, which have a strong and long-lasting vasoconstrictive effect. Three isoforms of endothelins coded by three different genes have been identified to date. Endothelin-1 (ET-1) is the most potent vasoconstrictive agent currently identified, and it was originally isolated and characterized from the culture media of aortic endothelial cells. Two other isoforms, named endothelin-2 (ET-2) and endothelin-3 (ET-3), were subsequently identified, along with structural homologues isolated from the venom ofActractapis engaddensis known as the sarafotoxins. The biological effects of endothelin production are determined via activation of one or two G-protein coupled receptors, endothelin receptors A (ETRA) and B (ETRB1 and ETRB2). Recently endothelin receptor C (ETRC) was discovered, however, its functions and distribution still remain unclear. The effects mediated by ET-1 via ETRA are vasoconstriction, bronchoconstriction and secretion of aldosterone. Agonists related to the ETRB1 activation cause vasodilatation by stimulating NO, PGI2 and endothelium-derived hyperpolarizing factor (EDHF). In contrast, coupling to ETRB2 causes vasoconstriction. Involvement of ET has been demonstrated in the pathophysiology of certain disorders. In this review, we discuss the physiological and pathophysiological role of endothelium-derived ET-1, the pharmacology of its two receptors, focusing on the role of ET-1 in the development of some pathophysiological conditions.
authors.affiliation: Clinical Department of Laboratory Diagnostics, Dubrava University Hospital, Zagreb, Croatia. aunic@kbd.hr
authors.forename: Adriana
authors.initials: A
authors.lastname: Unic
authors.forename: Lovorka
authors.initials: L
authors.lastname: Derek
authors.forename: Natasa
authors.initials: N
authors.lastname: Hodak
authors.forename: Domagoj
authors.initials: D
authors.lastname: Marijancevic
authors.forename: Marina
authors.initials: M
authors.lastname: Ceprnja
authors.forename: Tihana
authors.initials: T
authors.lastname: Serdar
authors.forename: Maja
authors.initials: M
authors.lastname: Krhac
authors.forename: Zeljko
authors.initials: Z
authors.lastname: Romic
mesh_terms: D000825:Animal Structures / Q000187:drug effects / Q000502:physiology; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D000072396:Endothelin-Converting Enzymes; D016232:Endothelins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology*; D006801:Humans; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D008954:Models, Biological; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D019255:NADPH Oxidases / Q000235:genetics; D017466:Receptors, Endothelin / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D014652:Vascular Diseases / Q000235:genetics; D014662:Vasoconstrictor Agents / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D016232:Endothelins; D017466:Receptors, Endothelin; D014662:Vasoconstrictor Agents; D019255:NADPH Oxidases; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes