Endothelin in vascular and endocrine systems: biological activities and its mechanisms of action

Endothelin family peptides are now known to exert diverse biological effects on a wide variety of tissues and cell types through at least two subtypes of receptors. In vascular systems, both ETA and ETB endothelin receptors present in vascular smooth muscle mediate the vasoconstrictor and mitogenic activities of the peptides, while ETB receptors in the endothelium mediate the vasodilator and antiplatelet activities. Endothelins also affect hormone secretion from a variety of endocrine organs including anterior and posterior pituitary, atria and adrenals. Endothelins activate the Ca(2+)-messenger system which involves both calmodulin and protein kinase C to exert their biological activities in almost all cell types examined, and appear to work in a paracrine and autocrine fashion. However, physiological and pathophysiological roles of endothelins are still incompletely understood and further studies are clearly required for elucidation of biological significance of this peptide family.