Biochemical and Biophysical Research Communications 1991-07-15

An endothelin receptor (ETA) antagonist isolated from Streptomyces misakiensis.

M Ihara, T Fukuroda, T Saeki, M Nishikibe, K Kojiri, H Suda, M Yano

Index: Biochem. Biophys. Res. Commun. 178 , 132, (1991)

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Abstract

A competitive endothelin (ET) antagonist, BE-18257B, was isolated from the fermentation products of Streptomyces misakiensis. It is a novel cyclic pentapeptide, cyclo(-D-Glu-L-Ala-allo-D-Ile-L-Leu-D-Trp-), and binds to ETA receptors (ET-1 selective) in cardiovascular tissues, but not to ETB receptors (equally sensitive to isopeptides of ET family) in kidney, adrenal gland and cerebellum tissues. BE-18257B also antagonizes ET-1-induced vasoconstriction in rabbit iliac artery and pressor action in rats. Thus it is a selective ETA antagonist and should provide a valuable tool for elucidation of the pharmacological and pathophysiological roles of ET-1.