Endothelin receptor family (IPR000499)
Short name: Endthln_rcpt
Overlapping homologous superfamilies
Endothelins are able to activate a number of signal transduction processes including phospholipase A2, phospholipase C and phospholipase D, as well as cytosolic protein kinase activation. The play an important role in the regulation of the cardiovascular system [PMID: 2451132, PMID: 11264479, PMID: 1916094] and are the most potent vasoconstrictors identified, stimulating cardiac contraction, regulating the release of vasoactive substances, and stimulating mitogenesis in blood vessels [PMID: 7647976, PMID: 9413859]. As a result, endothelins are implicated in a number of vascular diseases, including the heart, general circulation and brain [PMID: 11984741, PMID: 16529555, PMID: 1331845]. Endothelins stimulate the contraction in almost all other smooth muscles (e.g., uterus, bronchus, vas deferens, stomach) and stimulate secretion in several tissues e.g., kidney, liver and adrenals [PMID: 16340664, PMID: 8480469, PMID: 8466176]. Endothelins have also been implicated in a variety of pathophysiological conditions associated with stress including hypertension, myocardial infarction, subarachnoid haemorrhage and renal failure [PMID: 18758495].
Two endothelin receptor subtypes have been isolated and identified, endothelin A receptor(ETA) and endothelin B receptor (ETB) [PMID: 12037137, PMID: 1719979, PMID: 1849646, PMID: 1710450], and are members of the seven transmembrane rhodopsin-like G-protein coupled receptor family (GPCRA) which stimulate multiple effectors via several types of G protein [PMID: 7882989]. ETA and ETB receptors are both widely distributed, ETA receptors are mainly located on vascular smooth muscle cells, whereas ETB receptors are present on endothelial cells lining the vessel wall. Endothelin receptors have also been found in the brain, e.g. cerebral cortex, cerebellum and glial cells [PMID: 1847708, PMID: 2156267]. ETA receptors are considered to be the primary vasoconstrictor and growth-promoting receptor, and the binding of endothelin to ETA increases vasoconstriction (contraction of the blood vessel walls) and the retention of sodium, leading to increased blood pressure [PMID: 1351106]. Endothelin B receptor on the other hand not only inhibits cell growth and vasoconstriction in the vascular system but also functions as a "clearance receptor". This receptor-mediated clearance mechanism is particularly important in the lung, which clears about 80% of circulating endothelin-1 [PMID: 11067800, PMID: 11264479]. Both receptors are localised to non-vascular structures such as epithelial cells as well as occurring in the central nervous system (CNS) on glial cells and neurones, where they are thought to mediate neurotransmission and vascular functions [PMID: 9239759].
GO:0004962 endothelin receptor activity
GO:0016021 integral component of membrane
- PR00366 (ENDOTHELINR)