WS-7338, new endothelin receptor antagonists isolated from Streptomyces sp. No. 7338. II. Biological characterization and pharmacological characterization of WS-7338 B.
WS-7338, produced by Streptomyces sp. No. 7338, was found to be a competitive and specific antagonist against ET-1 receptors in in vitro studies and WS-7338 B is also active in vivo. Furthermore, WS-7338 B was a specific antagonist for vascular ET-1 receptors (ETA receptors) and significantly prevented the accumulation of intracellular inositol 1,4,5-triphosphate (IP3) in endothelin treated rat aorta tissues.
Miyata
S
S
Exploratory Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Ibaraki, Japan.
Hashimoto
M
M
Fujie
K
K
Nishikawa
M
M
Kiyoto
S
S
Okuhara
M
M
Kohsaka
M
M
D000818:Animals; D001011:Aorta / Q000378:metabolism; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D010456:Peptides, Cyclic / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors*; D017466:Receptors, Endothelin; D013552:Swine
D010456:Peptides, Cyclic; D011956:Receptors, Cell Surface; D017466:Receptors, Endothelin; C069764:cyclo(glutamyl-alanyl-isoleucyl-leucyl-tryptophyl)