Document Detail

Molecular pharmacology and pathophysiological significance of endothelin.
MedLine Citation:
PMID:  9015736     Owner:  NLM     Status:  MEDLINE    
Since the discovery of the most potent vasoconstrictor peptide, endothelin, in 1988, explosive investigations have rapidly clarified much of the basic pharmacological, biochemical and molecular biological features of endothelin, including the presence and structure of isopeptides and their genes (endothelin-1, -2 and -3), regulation of gene expression, intracellular processing, specific endothelin converting enzyme (ECE), receptor subtypes (ETA and ETB), intracellular signal transduction following receptor activation, etc. ECE was recently cloned, and its structure was shown to be a single transmembrane protein with a short intracellular N-terminal and a long extracellular C-terminal that contains the catalytic domain and numerous N-glycosylation sites. In addition to acute contractile or secretory actions, endothelin has been shown to exert long-term proliferative actions on many cell types. In this case, intracellular signal transduction appears to converge to activation of mitogen-activated protein kinase. As a recent dramatic advance, a number of non-peptide and orally active receptor antagonists have been developed. They, as well as current peptide antagonists, markedly accelerated the pace of investigations into the true pathophysiological roles of endogenous endothelin-1 in mature animals; e.g., hypertension, pulmonary hypertension, acute renal failure, cerebral vasospasm, vascular thickening, cardiac hypertrophy, chronic heart failure, etc. Thus, the interference with the endothelin pathway by either ECE-inhibition or receptor blockade may provide an exciting prospect for the development of novel therapeutic drugs.
K Goto; H Hama; Y Kasuya
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Japanese journal of pharmacology     Volume:  72     ISSN:  0021-5198     ISO Abbreviation:  Jpn. J. Pharmacol.     Publication Date:  1996 Dec 
Date Detail:
Created Date:  1997-05-28     Completed Date:  1997-05-28     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2983305R     Medline TA:  Jpn J Pharmacol     Country:  JAPAN    
Other Details:
Languages:  eng     Pagination:  261-90     Citation Subset:  IM    
Department of Pharmacology, University of Tsukuba, Ibaraki, Japan.
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MeSH Terms
Cardiovascular Diseases / physiopathology*
Endothelins / pharmacology*,  physiology*
Receptors, Endothelin / antagonists & inhibitors,  physiology
Reg. No./Substance:
0/Endothelins; 0/Receptors, Endothelin

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