MOLECULAR AND CELLULAR MECHANISM OF ENDOTHELIN REGULATION - IMPLICATIONS FOR VASCULAR FUNCTION

Endothelin (ET), a 21-amino acid peptide with potent vasoconstrictive activity, primarily produced by vascular endothelium is processed from a precursor, big endothelin, by an unknown converting enzyme. Three distinct endotheline designated as ET-1, ET-2, and ET-3 are now known to exist ubiquitously in various tissues. Possibly, the peptide plays many important physiological and pathophysiological roles in these tissues. Biological activities of the three ETs are slightly different with each other. Existence of three prototypes of ET-receptor were also demonstrated. The peptide stimulates phospholipase C and phospholipase A2 as well as calcium channels. Production and release of the peptide may be regulated by several vasoactive substances. Ultimate biological response induced by ET may be determined by the balance between ET-1 and ET-3 responses through those ET-receptors. Probably, endogenous ET regulates the vascular tonus in paracrine manner and plays some important role in hypertension and vasospasm although so far there is no direct evidence.