Beta-carbolines selectively antagonize the cholecystokinin action in isolated guinea-pig gallbladder muscle.
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.
D000478:Alkylation; D000818:Animals; D002243:Carbolines / Q000494:pharmacology*; D002766:Cholecystokinin / Q000037:antagonists & inhibitors*; D003983:Dibenzylchlorethamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005704:Gallbladder / Q000187:drug effects*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D011949:Receptors, Cholecystokinin / Q000187:drug effects
D002243:Carbolines; D011949:Receptors, Cholecystokinin; D003983:Dibenzylchlorethamine; C024915:beta-carboline-3-carboxylic acid ethyl ester; D002766:Cholecystokinin; C036150:beta-carboline-3-carboxylic acid methyl ester