WS009 A and B, new endothelin receptor antagonists isolated from Streptomyces sp. no. 89009. II. Biological characterization and pharmacological characterization of WS009 A and B.
WS009 A and B, produced by Streptomyces sp. No. 89009, were found to be competitive and specific antagonists against endothelin (ET)-1 receptors in in vitro studies and also active in in vivo studies. Furthermore, WS009 A and B were specific antagonists 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
Shouho
M
M
Sogabe
K
K
Kiyoto
S
S
Okuhara
M
M
Kohsaka
M
M
D000818:Animals; D000880:Anthraquinones / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000378:metabolism* / Q000494:pharmacology; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D007295:Inositol Phosphates / Q000378:metabolism; D008297:Male; D011817:Rabbits; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors*; D017466:Receptors, Endothelin; D014018:Tissue Distribution
D000880:Anthraquinones; D016232:Endothelins; D007295:Inositol Phosphates; D011956:Receptors, Cell Surface; D017466:Receptors, Endothelin; C076466:WS 009A; C076467:WS 009B