Biomedical subjects

V Nurchi

Publications and source records attributed to V Nurchi.

4 recordsLinked to original sources

PubMed1986

Enhancement of gamma-aminobutyric acid binding by quazepam, a benzodiazepine derivative with preferential affinity for type I benzodiazepine receptors.

We evaluated the effect of the two N-trifluoroethyl benzodiazepines, quazepam and its 2-oxo metabolite SCH 15725, which possess preferential affinity for type I benzodiazepine recognition sites, on the binding of [3H] gamma-aminobutyric acid ([3H]GABA) to rat brain membrane preparations. The study also included compounds such as diazepam and N-desalkyl-2-oxoquazepam (SCH 17514), which have equal affinity for the type I and type II receptor subtypes. Binding of [3H]GABA was studied in frozen-thawed and repeatedly washed cortical membranes incubated in 20 mM KH2PO4 plus 50 mM KCl, pH 7.4, at 4 degrees C in the absence and presence of quazepam or its metabolites. Addition of 10(-6) M quazepam increased by 30% specific [3H]GABA binding; as revealed by Scatchard plot analysis, the effect was due to an increase in the total number of GABA receptors. The effect of quazepam was concentration dependent, and it was shared by its active metabolite SCH 15725. The potency of quazepam and SCH 15725 in enhancing [3H]GABA binding was similar to that of diazepam, whereas CL 218872 and SCH 17514 were less active. Moreover, the [3H]GABA binding-enhancing effect of quazepam was mediated by an occupancy of benzodiazepine receptors, because it was specifically antagonized by 5 X 10(-6) M Ro15-1788.

Animals↗

PubMed1985

Changes in the characteristics of low affinity GABA binding sites elicited by Ro15-1788.

3H-GABA binding was studied in cortical membranes from cerebral cortex of handling-habituated and naive rats after the in vitro addition of Ro15-1788. At low concentrations (10(-8), 10(-9) M) Ro15-1788 increased the total number of low affinity 3H-GABA binding sites in brain tissue from naive rats but failed to modify 3H-GABA binding in tissue from handling-habituated ones. On the contrary, Ro15-1788 at higher concentrations (10(-5), 10(-6)M) decreased the total number of low affinity 3H-GABA binding sites in tissue from handling-habituated rats but failed to modify 3H-GABA binding in tissue from naive animals. Ro15-1788 (10(-7)M) failed to modify significantly low affinity 3H-GABA binding in membranes from both naive and handling-habituated rats. However, this concentration abolished the effect of beta-carbolines and diazepam on 3H-GABA binding in membranes from naive and handling-habituated rats, respectively. The changes in the affinity of 3H-GABA binding were inversely related to the changes in the number. The results suggest that: a) the action "in vitro" of Ro15-1788 on low affinity 3H-GABA binding depends from its concentration at the benzodiazepine recognition sites; b) the benzodiazepine recognition site has a modulatory role in the control of the function of GABA-ergic receptor. Our data might explain the conflicting results obtained with this compound "in vivo".

Animals↗

PubMed1984

Stress and beta-carbolines decrease the density of low affinity GABA binding sites; an effect reversed by diazepam.

Cerebral cortex membranes from rats habituated to manipulations preceding decapitation (habituated rats) had 40% higher GABA binding than membranes from naive animals. Diazepam (5 X 10(-6) M), added to membranes from naive rats, increased GABA binding to the level of habituated rats, but failed to induce any further increase in membranes from the latter animals. Vice versa, beta-carbolines (FG 7142, beta-CCE, DMCM) added to membranes from habituated rats lowered GABA binding to the level of naive animals, but caused no further decrease in the membranes from this last group. Diazepam removed the effect of beta-carbolines in membranes from habituated rats. It is suggested that handling represents a stressful stimulus for naive animals and that stress lowers GABA binding by releasing an endogenous ligand for benzodiazepine receptors possessing similar properties to beta-carbolines. Finally, the results indicate that the emotional status of animals from which brain tissue is obtained should be considered when connections between GABA and benzodiazepine receptors are studied.

Animals↗

PubMed1984

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.

Animals↗