The discovery, the present state, and the future prospects of endothelin.

Endothelin-1 (ET-1) is a potent vasoconstrictive peptide produced by endothelial cells of blood vessels. This peptide has quite a unique structure and pharmacological properties. ET-1 is produced in endothelial cells and may be secreted in a similar way to some paracrine hormones. The pressor response of ET-1 is largely ascribed to its direct vasoconstrictive activity. However, renin release induced by vasoconstriction of the renal artery and elevation of sympathetic tone via central nervous system stimulation by ET-1 are also possible causes of the pressor responses. ET-1 receptors and calcium channels are different. Activation of these receptors may stimulate calcium stores via phosphatidylinositol (PI) turnover, inducing a transient increase of intracellular free calcium as well as initiating a calcium influx via the cell membrane calcium channel. The latter calcium influx induces the sustained increase of intracellular calcium ion and contracture. Recent experimental results suggest the possibility that ET has extracardiovascular activities in addition to its cardiovascular effect, i.e., it may be a neuropeptide or a neurosecretory hormone. ET-1 is also a cell-growth factor.