Evidence for an involvement of GABA receptors in the mediation of the proconvulsant action of ethyl-beta-carboline-3-carboxylate.
The kinetic characteristics of binding of [3H]-GABA and the pattern of isoniazid-induced convulsions were studied in rats treated with repeated intraventricular injections of ethyl-beta-carboline-3-carboxylate (beta-CCE) (10 micrograms/rat, twice daily for 8 days). Thirty-six hours after the last injection, the total number of binding sites for [3H]-GABA was decreased (25%) in the cerebral cortex and hippocampus. On the other hand, there was no significant difference in the dissociation constant (KD) between beta-CCE and solvent-treated rats. The decrease in binding sites for [3H]-GABA was paralleled by a strong potentiation of the convulsant pattern elicited by isoniazid. The results suggest that the proconvulsant effect elicited by beta-CCE is mediated by the decrease in the total number of binding sites for GABA, secondary to the interaction between beta-CCE and the benzodiazepine receptor coupled to the GABA receptor.
D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D002243:Carbolines / Q000008:administration & dosage / Q000633:toxicity*; D002540:Cerebral Cortex / Q000378:metabolism*; D004357:Drug Synergism; D006624:Hippocampus / Q000378:metabolism*; D007211:Indoles / Q000633:toxicity*; D007276:Injections, Intraventricular; D007538:Isoniazid / Q000633:toxicity; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D011963:Receptors, GABA-A; D012640:Seizures / Q000139:chemically induced* / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D002243:Carbolines; D007211:Indoles; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; C024915:beta-carboline-3-carboxylic acid ethyl ester; D007538:Isoniazid