Tetronothiodin, a novel cholecystokinin type-B receptor antagonist produced by Streptomyces sp. NR0489. II. Isolation, characterization and biological activities.
A novel cholecystokinin type-B receptor antagonist named tetronothiodin has been isolated by column chromatography and preparative HPLC from the fermentation broth of Streptomyces sp. NR0489. Tetronothiodin inhibited the binding of CCK8 (C-terminal octapeptide of cholecystokinin) to rat cerebral cortex membranes (CCK type-B receptors) with an IC50 of 3.6 nM, whereas it did not inhibit CCK8 binding to rat pancreatic membranes (CCK type-A receptors). It also inhibited CCK8 induced Ca2+ mobilization in GH3 cells, a rat anterior pituitary cell line, but was without effect on the basal cytosolic Ca2+ concentration. This finding indicated tetronothiodin was an antagonist of CCK type-B receptors.
Ohtsuka
T
T
Nippon Roche Research Center, Kamakura, Japan.
Kotaki
H
H
Nakayama
N
N
Itezono
Y
Y
Shimma
N
N
Kudoh
T
T
Kuwahara
T
T
Arisawa
M
M
Yokose
K
K
Seto
H
H
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002540:Cerebral Cortex / Q000187:drug effects; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D005663:Furans / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D010179:Pancreas / Q000187:drug effects; D010903:Pituitary Gland, Anterior / Q000187:drug effects; D051381:Rats; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*; D012844:Sincalide / Q000037:antagonists & inhibitors; D013291:Streptococcus / Q000737:chemistry*; D013876:Thiophenes / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology
D005663:Furans; D011949:Receptors, Cholecystokinin; D013876:Thiophenes; C073565:tetronothiodin; D012844:Sincalide; D002118:Calcium