Modulation of [3H]Muscimol Binding in Rat Cerebellar and Cerebral Cortical Membranes by Picrotoxin, Pentobarbitone, and Etomidate

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Abstract
Modulation of [3H]muscimol binding by picrotoxin, pentobarbitone, and etomidate was investigated in rat cerebellar and cerebral cortical membranes. In cerebellum, at 37°C in the presence of chloride ions (150 mM), picrotoxin and picrotoxinin decreased specific [3H]-muscimol binding to 43 ± 3% of control, with an EC50 of 1.2 ± 0.1 μM. [3H]Muscimol saturation experiments in the presence and absence of picrotoxin indicated that the picrotoxin effect was primarily due to a loss of high-affinity muscimol sites with KD∼ 10 nM. Pentobarbitone enhanced specific [3H]muscimol binding to 259 ± 3% of control, with EC50= 292 ± 37 μM, and etomidate increased binding to 298 ± 18%, with EC50= 7.1 ± 1.0 μM. The influence of temperature and chloride ion concentration on these effects was investigated by comparing experiments at 37 and 0°C in the presence or absence of chloride at constant ionic strength. The results indicate that studies at 0°C underestimate the coupling between GABA receptors and barbiturate sites and that they greatly overestimate the importance of chloride ions in this phenomenon. In cerebral cortical membranes (37°C, 150 mM Cl−), the effect of picrotoxin was similar to that observed in cerebellum, whereas the effects of pentobarbitone and etomidate were greater, but occured at higher concentrations.