β-Carbolines Selectively Antagonize the Cholecystokinin Action in Isolated Guinea-Pig Gallbladder Muscle

Abstract

Abstract-Two(3-carbolines, methyl (3-carboline-3-carboxylate (8-CCM) and ethyl , caused the parallel shift of the dose response curve for cholecystokinin (CCK) in isolated guinea-pig gallbladder muscle. The Schild plot regarding the parallel shift in the dose-response curves had a regression line with a slope of 1.03 and a pA2 value of 5.17 for l3-CCE, while the method of van Rossum gave a pA2 value of 5.24 for (3-CCE and 5.53 for 3-CCM. Both the (3-carbolines protected CCK receptors in the gallbladder muscle from alkylation by dibenamine, but 9-CCM did not protect acetylcholine receptors from dibenamine alkylation.These results suggest that 9-CCM and 3-CCE, so-called inverse agonists of benzodiazepines (BZP), antagonize the CCK action in the gallbladder muscle in a competitive manner, and the antagonism takes place at CCK receptor sites.No spare receptors for CCK were found in the guinea-pig gallbladder muscle.