Interaction of pentobarbital with gabaergic drugs acting on the Cl−-ATPase activity of the plasma membranes from bream brain (Abramis brama L.)

Abstract

The present study was designed to investigate the role of the interaction of pentobarbital with γ-aminobutyric acid (GABA)ergic drugs acting on the Cl−-adenosine triphosphate (ATP)ase activity of the plasma membranes fraction of bream brain. The preincubation and then incubation of the membranes with pentobarbital as well as with other GABAergic ligands was conducted at physiologic pH (7.4), i.e. at the condition where the Cl−-ATPase activity is not detected. Pentobarbital (1–100 μM) induces Cl−-ATPase activity, however at high concentration (1000 μM) no effect of the ligand was found. In addition pentobarbital (50 μM) enhances the effect of low concentration of GABA (1 μM) on the Cl−-ATPase activity, but inhibits the action of high concentration of GABA (100 μM) on the enzyme. Whereas no activating effect of pentobarbital in the presence of baclofen (1 μM) was found. The blocker of GABAA-receptors, picrotoxin (50 μM) and bicuculline (5 μM) eliminated the action of pentobarbital on the enzyme. The present results provide evidence for the first time that at physiologic pH in incubation medium the interaction of pentobarbital with GABAergic drugs on the Cl−-ATPase activity is similar to the effects of these ligands on the GABAA-receptor.