1991 Volume 32 Issue 4 Pages 411-418
Effects of diazepam on the binding of γ-aminobutyric acid (GABA) in membranes obtained from brains of acute ischemic hepatic failure rats (AHFR) were studied.
In membranes prepared from brains of control rats, GABA binding was maximally enhanced by 14% at 10-12M diazepam, while not enhanced at 10-15-10-13M diazepam. At concentrations of diazepam higher than 10-12M, enhancement of GABA binding was reduced. In membranes prepared from brains of AHFR, GABA binding was not affected at 10-15-10-13M diazepam, but was enhanced by 7% at 10-12 M, 32% at 10-11M, and maximally enhanced by 34% at 10-10-10-8M. Scatchard plot analysis revealed that the effect was due to an increase in the affinity of the low affinity site in membranes prepared from brains of control rats. In membranes prepared from brains of AHFR, the effect was due to an increase in both the affinity and the density of the low affinity site. The stimulation of GABA binding by diazepam in membranes prepared from brains of both control rats and AHFR was significantly inhibited by Ro 15-1788, a selective competitive antagonist of diazepam. The degree of the enhancement in GABA binding by diazepam was significantly higher in AHFR when compared with control rats. These results suggest that the alterations of GABA-benzodiazepine receptor complex exist in AHFR and may possibly be associated with hepatic encephalopathy.
