There are at least four known endothelin receptors, ETA, ETB1, ETB2 and ETC,[1] all of which are G protein-coupled receptors whose activation result in elevation of intracellular-free calcium,[2] which constricts the smooth muscles of the blood vessels, raising blood pressure, or relaxes the smooth muscles of the blood vessels, lowering blood pressure, among other functions.
ETA is a subtype for vasoconstriction[1] These receptors are found in the smooth muscle tissue of blood vessels, and binding of endothelin to ETA increases vasoconstriction (contraction of the blood vessel walls) and the retention of sodium, leading to increased blood pressure.[3]
Widely distributed in the body, receptors for endothelin are present in blood vessels and cells of the brain, choroid plexus and peripheral nerves. When applied directly to the brain of rats in picomolar quantities as an experimental model of stroke, endothelin-1 caused severe metabolic stimulation and seizures with substantial decreases in blood flow to the same brain regions, both effects mediated by calcium channels.[5]
A similar strong vasoconstrictor action of endothelin-1 was demonstrated in a peripheral neuropathy model in rats.[6]
^ abcdeMedical physiology a cellular and molecular approach (2nd ed., International ed.). Philadelphia, PA: Saunders/Elsevier. 2009. p. 480. ISBN9781437720174.|first1= missing |last1= in Authors list (help)
^Davenport AP (2002). "International Union of Pharmacology. XXIX. Update on endothelin receptor nomenclature". Pharmacol. Rev.54 (2): 219–26. doi:10.1124/pr.54.2.219. PMID12037137.
^Hynynen MM, Khalil RA; Khalil (January 2006). "The vascular endothelin system in hypertension--recent patents and discoveries". Recent Pat Cardiovasc Drug Discov1 (1): 95–108. doi:10.2174/157489006775244263. PMC: 1351106. PMID17200683.
^Barnes K, Turner AJ; Turner (August 1997). "The endothelin system and endothelin-converting enzyme in the brain: molecular and cellular studies". Neurochem. Res.22 (8): 1033–40. doi:10.1023/A:1022435111928. PMID9239759.
^Gross PM, Zochodne DW, Wainman DS, Ho LT, Espinosa FJ, Weaver DF; Zochodne; Wainman; Ho; Espinosa; Weaver (July 1992). "Intraventricular endothelin-1 uncouples the blood flow: metabolism relationship in periventricular structures of the rat brain: involvement of L-type calcium channels". Neuropeptides22 (3): 155–65. doi:10.1016/0143-4179(92)90158-S. PMID1331845.CS1 maint: Multiple names: authors list (link)
^Verheij JB, Kunze J, Osinga J, van Essen AJ, Hofstra RM; Kunze; Osinga; Van Essen; Hofstra (2002). "ABCD syndrome is caused by a homozygous mutation in the EDNRB gene". Am. J. Med. Genet.108 (3): 223–5. doi:10.1002/ajmg.10172. PMID11891690.CS1 maint: Multiple names: authors list (link)