An endothelin receptor (ETA) antagonist isolated from Streptomyces misakiensis.
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.
Ihara
M
M
Central Research and Exploratory Research Labs., Banyu Pharmaceutical Co., Ltd., Tokyo, Japan.
Fukuroda
T
T
Saeki
T
T
Nishikibe
M
M
Kojiri
K
K
Suda
H
H
Yano
M
M
D000818:Animals; D001011:Aorta / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002478:Cells, Cultured; D016232:Endothelins / Q000378:metabolism / Q000494:pharmacology*; D007083:Iliac Artery / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009928:Organ Specificity; D010456:Peptides, Cyclic / Q000302:isolation & purification / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D011921:Rats, Inbred WKY; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000378:metabolism; D017466:Receptors, Endothelin; D013302:Streptomyces; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D016232:Endothelins; D010456:Peptides, Cyclic; D011956:Receptors, Cell Surface; D017466:Receptors, Endothelin; D014665:Vasodilator Agents; C069764:cyclo(glutamyl-alanyl-isoleucyl-leucyl-tryptophyl)