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The FASEB Journal, Vol 5, 2713-2720, Copyright © 1991 by The Federation of American Societies for Experimental Biology
REVIEWS |
GM Rubanyi and LH Botelho
Berlex Laboratories, Inc., Cedar Knolls, New Jersey 07927.
The discovery of endothelium-derived relaxing (prostacyclin, EDRF) and contracting factors (EDCF) in the past decade opened up new vistas not only for basic and clinical research, but revolutionized our thinking about regulation and control of the cardiovascular system in health and disease. One of the most exciting developments in recent years was the discovery of a peptidergic EDCF and its isolation and identification as a unique 21-amino-acid peptide, endothelin (ET). This review summarizes the state-of-the-art in some areas of this fast-moving field, including the biosynthesis, tissue-specific expression, and binding of ET isoforms. Recent information about the nature of endothelin-converting enzyme (ECE) and the cloning, sequencing, and expression of ET receptor subtypes will be discussed. Based on current knowledge of the wide variety of biological actions of ETs, working hypotheses are presented about the possible autocrine, paracrine, and humoral actions of ETs and their potential role in modulating cardiovascular functions. In addition, the proposed significance of ETs in human cardiovascular diseases is summarized. In spite of the abundance of studies generated over the past 3 years and the postulated working hypotheses based on these findings, the true significance of ETs in short- and long-term regulation/modulation of tissue function remains to be determined. This will be the task of future investigations, using more sensitive detection methods and selective inhibitors of the biosynthesis and actions of ETs.
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