Influence of plasma dialysate from normal and renal dysfunction rats on the electroencephalogram and gamma-aminobutyric acid A receptor complex modulation of thiopental.
We have previously reported that brain sensitivity to thiopental with respect to electroencephalogram (EEG) is enhanced in uranyl acetate pretreated renal dysfunction rats. The results were attributed to pharmacodynamic factors. In this study, in vivo EEG and in vitro binding studies for gamma-aminobutyric acid (GABA)-benzodiazepine receptor complex were performed to investigate the mechanism of the enhanced effect of thiopental. The receptor binding properties in the brain membrane from normal and renal dysfunction rats were examined using [3H]tertbutylbicycloorthobenzoate (TBOB), [3H]flunitrazepam and [3H]muscimol. The effect of plasma dialysate from normal (ND) and renal dysfunction rats (RDD) on the thiopental induced EEG and receptor binding were also examined to confirm the role of endogenous compounds. The intrinsic receptor binding characteristics of various sites and their allosteric interaction with thiopental was similar in membrane preparations from normal and renal dysfunction rats. However, RDD, when compared to ND, enhanced the EEG induced by thiopental. At the receptor level, RDD significantly enhanced the thiopental induced inhibition of TBOB. No difference was found between the influence of ND and RDD on the interaction between thiopental and flunitrazepam or muscimol binding. These results showed that the thiopental induced allosteric inhibition of TBOB binding was potentiated by some endogenous compounds in RDD and suggests that this action might be the mechanism, at least in part, for the increased sensitivity of thiopental in renal dysfunction rats.
Srivastava
K
K
Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
Hatanaka
T
T
Katayama
K
K
Koizumi
T
T
D000818:Animals; D003956:Dialysis; D004353:Drug Evaluation, Preclinical; D004569:Electroencephalography; D005445:Flunitrazepam / Q000378:metabolism; D018757:GABA Modulators / Q000494:pharmacology*; D007674:Kidney Diseases / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D009118:Muscimol / Q000378:metabolism; D010949:Plasma / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects*; D012016:Reference Values; D013874:Thiopental / Q000494:pharmacology*
D018757:GABA Modulators; D011963:Receptors, GABA-A; D009118:Muscimol; D005445:Flunitrazepam; D013874:Thiopental