title: Functional coupling of GABAA receptors and benzodiazepine recognition site subtypes in the spinal cord of the rat.
abstract: The interaction between GABAA receptors and benzodiazepine (BZD) recognition site subtypes in the spinal cord of the rat was investigated. Computer analysis of displacement curves for [3H]flunitrazepam [( 3H]FNT) binding by 2-oxo-quazepam (2OXOQ) indicated the presence of two subtypes of BZD recognition sites in this region. Type I sites accounted for approximately 25% of the total number of BZD recognition sites, the remainder being Type II sites. A similar proportion of Type I and Type II sites was obtained by Scatchard analysis of the saturation curves for [3H]FNT, [3H]2OXOQ and [3H]ethyl-beta-carboline-3-carboxylate [( 3H]beta CCE) binding. The in vitro addition of GABA (10(-8)-10(-4) M) to spinal cord membrane preparations produced an increase in the binding of [3H]FNT and [3H]2OXOQ. The maximal enhancement produced by GABA was 50 and 82% above control values for [3H]FNT and [3H]2OXOQ, respectively. In contrast, GABA stimulated both [3H]FNT and [3H]2OXOQ binding in the cerebellum to a similar extent. We also evaluated the effects of different ligands for BZD recognition sites on the binding of [3H]GABA to spinal cord membranes, as compared with brain areas containing a higher proportion ( greater than 30%) of Type I sites. Diazepam, quazepam and the beta-carboline, ZK 93423, enhanced the specific binding of [3H]GABA in a concentration-dependent manner (10(-7)-10(-5) M) in the cerebral cortex and hippocampus but not in the spinal cord and cerebellum. These results indicate that there is a regional variation in the interaction between GABA and BZD recognition sites in the central nervous system.
authors.affiliation: Department of Experimental Biology, University of Cagliari, Italy.
authors.forename: M G
authors.initials: MG
authors.lastname: Corda
authors.forename: O
authors.initials: O
authors.lastname: Giorgi
authors.forename: B
authors.initials: B
authors.lastname: Longoni
authors.forename: E
authors.initials: E
authors.lastname: Ongini
authors.forename: G
authors.initials: G
authors.lastname: Pesce
authors.forename: R
authors.initials: R
authors.lastname: Cruciani
authors.forename: G
authors.initials: G
authors.lastname: Biggio
mesh_terms: D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008566:Membranes / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D011963:Receptors, GABA-A; D001569:Benzodiazepines; D005680:gamma-Aminobutyric Acid