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

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Abstract
Two .beta.-carbolines, methyl .beta.-carboline-3-carboxylate (.beta.-CCM) and ethyl .beta.-carboline-3-carboxylate (.beta.-CCE), 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 .beta.-CCE, while the method of van Rossum gave a pA2 value of 5.24 for .beta.-CCE and 5.53 for .beta.-CCM. Both the .beta.-carbolines protected CCK receptors in the gallbladder muscle from alkylation by dibenamine, but .beta.-CCM did not protect acetylcholine receptors from dibenamine alkylation. These results suggest that .beta.-CCM and .beta.-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.