Contrasting effects of ethyl beta-carboline-3-carboxylate (beta CCE) and diazepam on cerebellar cyclic GMP content and antagonism of both effects by Ro 15-1788, a specific benzodiazepine receptor blocker.
Ethyl beta-carboline-3-carboxylate (beta CCE), a benzodiazepine antagonist, was found to increase basal levels of cyclic GMP in rat cerebellum. beta CCE also augmented the elevation of cyclic GMP concentrations induced by isoniazid, in contrast to diazepam which blocked this effect of isoniazid. Administration of beta CCE and diazepam together cancelled each other's effect on the elevation of cyclic GMP levels after isoniazid. Ro 15-1788, another potent benzodiazepine antagonist, was found to have virtually no effect on cyclic GMP levels in naive or isoniazid-treated rats. Ro 15-1788 antagonized diazepam's lowering of the elevation of cyclic GMP content of cerebellum after isoniazid. Ro 15-1788 also blocked the increase in cyclic GMP levels elicited by beta CCE, indicating that this effect of beta CCE involves its interaction at benzodiazepine receptors. Some pharmacological actions of beta CCE might be based on hindering GABA transmission.
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology*; D002243:Carbolines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D003975:Diazepam / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005442:Flumazenil; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D007538:Isoniazid / Q000494:pharmacology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000187:drug effects; D011963:Receptors, GABA-A
D001570:Benzodiazepinones; D002243:Carbolines; D007211:Indoles; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D005442:Flumazenil; C024915:beta-carboline-3-carboxylic acid ethyl ester; D006152:Cyclic GMP; D003975:Diazepam; D007538:Isoniazid