Binding of 3H-DMCM to benzodiazepine receptors; chloride dependent allosteric regulation mechanisms.
DMCM is a convulsant agent with negative efficacy at benzodiazepine (BZ) receptors. 3H-DMCM binds to benzodiazepine receptors in vitro. The sensitivity of 3H-DMCM binding to agents presumed to act on chloride channels associated with the BZ/GABA-receptor-complex was investigated at 37 degrees C. Chloride ions (200 mM) enhanced the specific binding of 3H-DMCM four-fold. Similarly the specific binding of 3H-DMCM was enhanced by picrotoxinine in the absence but not in the presence of chloride ions. (+)-Etomidate and pentobarbital reduced the specific 3H-DMCM binding in a partially chloride ion dependent and picrotoxinine sensitive manner. The results obtained are consonant with the idea that 3H-DMCM binds to the BZ/GABA-receptor-chloride ionophor complex; furthermore, binding of 3H-DMCM seems to involve a chloride dependent allosteric regulation mechanism.
D000818:Animals; D000838:Anions / Q000494:pharmacology; D002243:Carbolines / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism*; D002712:Chlorides / Q000502:physiology*; D005045:Etomidate / Q000494:pharmacology; D007211:Indoles / Q000378:metabolism*; D008968:Molecular Conformation; D010424:Pentobarbital / Q000494:pharmacology; D010852:Picrotoxin / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism* / Q000502:physiology; D011963:Receptors, GABA-A; D054830:Sesterterpenes
D000838:Anions; D002243:Carbolines; D002712:Chlorides; D005045:Etomidate; D007211:Indoles; D010424:Pentobarbital; D010852:Picrotoxin; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D054830:Sesterterpenes; C034818:methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate; C022961:picrotoxinin