Endothelin-1: Small Molecules and Peptides

Endothelin-1 (ET-1) is a vascular endothelium derived peptide that acts as a potent vasoconstrictor. It is processed by a furin-like protease to yield a peptide termed Big ET-1. Big ET-1 is then cleaved by ECE-1, producing the mature form ET-1 (1-21). ET-1 expression is induced by mechanical stimulation, various hormones, and pro-inflammatory cytokines. Its production is inhibited by nitric oxide, prostacyclin, and atrial natriuretic peptide (ANP). ET-1 exerts its vasoconstrictor effects primarily through the receptor ETA on vascular smooth muscle cells. It also acts through the ETB receptor on vascular smooth muscle and endothelial cells. ET-1 additionally stimulates cardiac myocyte proliferation and contractility, regulates secretion by hypothalamic and pituitary cells, and promotes neutrophil extravasation and activation.