Cholecystokinin antagonism by anthramycin, a benzodiazepine antibiotic, in the central nervous system in mice.

Anthramycin (ATM) which is a product of some streptomyces micro-organisms was shown to antagonize the central effects of cholecystokinin (CCK) such as antinociception and satiety and to displace CCK bound to the slices from the brains of mice. Sulfated octapeptide CCK (CCK8) was administered intracisternally to mice at doses of 1 microgram/mouse for inducing antinociception and 200 ng/mouse for satiety. ATM was administered intraperitoneally to mice at doses such as 0.3 and 0.5 mg/kg. CCK8-induced antinociception and satiety were significantly reversed by ATM in those doses. [125I]CCK8 binding to the brain slices was observed autoradiographically. The autoradiograms from the slices were converted to false color images by using a microcomputer. The radioactivity in the autoradiograms was expressed by color spectra in the false color images. Comparison of the binding of [125I]CCK8 to the brain slices in the presence and the absence of ATM revealed that ATM (10(-6) M) clearly displaced the CCK8 binding in the various regions, especially in the cortex, of the brain. These findings suggest that ATM acts as an potent antagonist of CCK in the central nervous system in mice.