Tetronothiodin, a novel cholecystokinin type-B receptor antagonist produced by Streptomyces sp. NR0489. II. Isolation, characterization and biological activities.

Abstract

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.