title: Modulation of the GABA autoreceptor by benzodiazepine receptor ligands.
abstract: The effects of various benzodiazepine receptor ligands on the GABA autoreceptor have been studied in slices of cerebral cortex of the rat. The GABAA receptor agonist muscimol inhibited the K+-stimulated release of [3H]GABA with a pIC25 of 7.65 +/- 0.11. This effect was antagonised by the GABAA receptor antagonist bicuculline, which had an IC50 of 0.36 +/- 0.03 microM. Small concentrations (less than 1 microM) of the benzodiazepine full agonist clonazepam did not significantly alter K+-evoked release of [3H]GABA but shifted the concentration-effect curve for muscimol to the left. This effect was blocked by the benzodiazepine antagonist flumazenil. By contrast, the benzodiazepine full inverse agonist methyl beta-carboline-3-carboxylate shifted the muscimol concentration-effect curve to the right and this too was blocked by flumazenil. The results suggest that the GABA autoreceptor in cortical slices from the rat is modulated by a benzodiazepine receptor.
authors.affiliation: Department of Biomedical Research, Wyeth Research Ltd, Berkshire, U.K.
authors.forename: C
authors.initials: C
authors.lastname: Ennis
authors.forename: M C
authors.initials: MC
authors.lastname: Minchin
mesh_terms: D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002243:Carbolines / Q000494:pharmacology*; D002998:Clonazepam / Q000494:pharmacology*; D005442:Flumazenil / Q000494:pharmacology*; D008024:Ligands; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects*
chemical_list: D002243:Carbolines; D008024:Ligands; D011963:Receptors, GABA-A; C026072:1-methyl-beta-carboline-3-carboxylic acid; D009118:Muscimol; D005442:Flumazenil; D002998:Clonazepam; D001640:Bicuculline