Endothelin-1 and the regulation of vascular tone.
1. In 1988, Yanagisawa et al. reported the presence of a potent peptide from the supernatant of porcine endothelial cells. This was later named endothelin-1 (ET-1) and was found to belong to a new family of vasoconstrictor peptides. There are at least three isoforms of endothelin: ET-1, endothelin-2 and endothelin-3. 2. ET-1 is produced from a larger precursor molecule by endothelin converting enzyme (ECE); there may be a number of ECE but the most physiologically relevant appears to be a membrane-bound neutral metalloprotease. The endothelin precursor is produced on demand and is regulated at the mRNA level. 3. Two subtypes of mammalian endothelin receptors have been cloned and sequenced: ETA receptors which mediate vasoconstriction and ETB receptors which mediate both vasoconstriction and vasodilatation. However, functional studies have indicated that other subtypes of endothelin receptors may exist. 4. ET-1 has a wide range of biological actions apart from its direct effects on vascular tone, including constriction of non-vascular smooth muscle, cardiac effects, mitogenesis and stimulation of the release of hormones such as atrial natriuretic peptide and prostacyclin. At low concentrations which have no direct vasoconstrictor action, ET-1 potentiates the effect of other vasoconstrictor agonists. 5. The precise role of ET-1 in health and disease is not well defined at present; however, there are indications that it may have a role in the pathogenesis of some cardiovascular disease states, including subarachnoid haemorrhage, renal ischaemia and certain types of hypertension.
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Department of Medical Laboratory Science, Royal Melbourne Institute of Technology, Victoria, Australia.
Reid
J J
JJ
D000595:Amino Acid Sequence; D000818:Animals; D002318:Cardiovascular Diseases / Q000209:etiology; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000737:chemistry / Q000494:pharmacology / Q000502:physiology*; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D017466:Receptors, Endothelin / Q000819:agonists*; D015398:Signal Transduction / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D017466:Receptors, Endothelin