PR00366

ENDOTHELINR

PRINTS entry
Member databasePRINTS
PRINTS typefamily
Short nameENDOTHELINR

Description
Imported from IPR000499

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
[21, 22, 1]
and are the most potent vasoconstrictors identified, stimulating cardiac contraction, regulating the release of vasoactive substances, and stimulating mitogenesis in blood vessels
[17, 18]
. As a result, endothelins are implicated in a number of vascular diseases, including the heart, general circulation and brain
[20, 5, 3]
. 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
[7, 6, 10]
. Endothelins have also been implicated in a variety of pathophysiological conditions associated with stress including hypertension, myocardial infarction, subarachnoid haemorrhage and renal failure
[19]
.

Two endothelin receptor subtypes have been isolated and identified, endothelin A receptor(ETA) and endothelin B receptor (ETB)
[12, 9, 14, 11]
, 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
[4]
. 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
[8, 13]
. 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
[2]
. 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
[16, 22]
. 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
[15]
.

References
Imported from IPR000499

1.Endothelins. Rubanyi GM, Botelho LH. FASEB J. 5, 2713-20, (1991). View articlePMID: 1916094

2.Symposium on Compensatory Mechanisms and their Limitations in Heart Failure. 55th annual scientific session of the Japanese Circulation Society. Kyoto, March 31, 1991. Jpn. Circ. J. 56, 453-526, (1992). PMID: 1351106

3.Intraventricular endothelin-1 uncouples the blood flow: metabolism relationship in periventricular structures of the rat brain: involvement of L-type calcium channels. Gross PM, Zochodne DW, Wainman DS, Ho LT, Espinosa FJ, Weaver DF. Neuropeptides 22, 155-65, (1992). View articlePMID: 1331845

4.Molecular identification of guanine-nucleotide-binding regulatory proteins which couple to endothelin receptors. Takigawa M, Sakurai T, Kasuya Y, Abe Y, Masaki T, Goto K. Eur. J. Biochem. 228, 102-8, (1995). View articlePMID: 7882989

5.Pharmacology and physiopathology of the brain endothelin system: an overview. Schinelli S. Curr. Med. Chem. 13, 627-38, (2006). View articlePMID: 16529555

6.Stimulation of mitogenesis in human thyroid epithelial cells by endothelin. Eguchi K, Kawakami A, Nakashima M, Ida H, Sakito S, Sakai M, Terada K, Kawabe Y, Fukuda T, Ishikawa N. Acta Endocrinol. 128, 215-20, (1993). PMID: 8480469

7.The renal medullary endothelin system in control of sodium and water excretion and systemic blood pressure. Kohan DE. Curr. Opin. Nephrol. Hypertens. 15, 34-40, (2006). View articlePMID: 16340664

8.Endothelin in human brain and pituitary gland: presence of immunoreactive endothelin, endothelin messenger ribonucleic acid, and endothelin receptors. Takahashi K, Ghatei MA, Jones PM, Murphy JK, Lam HC, O'Halloran DJ, Bloom SR. J. Clin. Endocrinol. Metab. 72, 693-9, (1991). PMID: 1847708

9.Cloning and characterization of cDNA encoding human A-type endothelin receptor. Adachi M, Yang YY, Furuichi Y, Miyamoto C. Biochem. Biophys. Res. Commun. 180, 1265-72, (1991). View articlePMID: 1719979

10.Endothelin peptides and the kidney. Simonson MS, Dunn MJ. Annu. Rev. Physiol. 55, 249-65, (1993). View articlePMID: 8466176

11.Cloning and sequence analysis of a cDNA encoding human non-selective type of endothelin receptor. Nakamuta M, Takayanagi R, Sakai Y, Sakamoto S, Hagiwara H, Mizuno T, Saito Y, Hirose S, Yamamoto M, Nawata H. Biochem. Biophys. Res. Commun. 177, 34-9, (1991). View articlePMID: 1710450

12.International Union of Pharmacology. XXIX. Update on endothelin receptor nomenclature. Davenport AP. Pharmacol. Rev. 54, 219-26, (2002). View articlePMID: 12037137

13.Endothelin in brain: receptors, mitogenesis, and biosynthesis in glial cells. MacCumber MW, Ross CA, Snyder SH. Proc. Natl. Acad. Sci. U.S.A. 87, 2359-63, (1990). View articlePMID: 2156267

14.Cloning and functional expression of a vascular smooth muscle endothelin 1 receptor. Lin HY, Kaji EH, Winkel GK, Ives HE, Lodish HF. Proc. Natl. Acad. Sci. U.S.A. 88, 3185-9, (1991). View articlePMID: 1849646

15.The endothelin system and endothelin-converting enzyme in the brain: molecular and cellular studies. Barnes K, Turner AJ. Neurochem. Res. 22, 1033-40, (1997). View articlePMID: 9239759

16.Endothelins and endothelin receptor antagonists: therapeutic considerations for a novel class of cardiovascular drugs. Luscher TF, Barton M. Circulation 102, 2434-40, (2000). PMID: 11067800

17.ETA receptor-mediated constrictor responses to endothelin peptides in human blood vessels in vitro. Maguire JJ, Davenport AP. Br. J. Pharmacol. 115, 191-7, (1995). PMID: 7647976

18.Contribution of endogenous endothelin-1 to the maintenance of vascular tone: role of nitric oxide. Gellai M, De Wolf R, Fletcher T, Nambi P. Pharmacology 55, 299-308, (1997). PMID: 9413859

19.Endothelin: 20 years from discovery to therapy. Barton M, Yanagisawa M. Can. J. Physiol. Pharmacol. 86, 485-98, (2008). View articlePMID: 18758495

20.Role of endothelin in cardiovascular disease. Agapitov AV, Haynes WG. J Renin Angiotensin Aldosterone Syst 3, 1-15, (2002). PMID: 11984741

21.A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Yanagisawa M, Kurihara H, Kimura S, Tomobe Y, Kobayashi M, Mitsui Y, Yazaki Y, Goto K, Masaki T. Nature 332, 411-5, (1988). View articlePMID: 2451132

22.Endothelin system: the double-edged sword in health and disease. Kedzierski RM, Yanagisawa M. Annu. Rev. Pharmacol. Toxicol. 41, 851-76, (2001). View articlePMID: 11264479

Supplementary References

1. G protein involvement in receptor-effector coupling. Casey PJ, Gilman AG. J. Biol. Chem. 263, 2577-80, (1988). View articlePMID: 2830256

2. Design of a discriminating fingerprint for G-protein-coupled receptors. Attwood TK, Findlay JB. Protein Eng. 6, 167-76, (1993). View articlePMID: 8386361

3. Fingerprinting G-protein-coupled receptors. Attwood TK, Findlay JB. Protein Eng. 7, 195-203, (1994). View articlePMID: 8170923

4. G proteins in signal transduction. Birnbaumer L. Annu. Rev. Pharmacol. Toxicol. 30, 675-705, (1990). View articlePMID: 2111655

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