Effects of intravenous anesthetics on the activities of various ATPases in rat brain

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  • ラット脳各種ATPase活性に対する静脈麻酔薬の作用

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Abstract

This study examined whether the activity of magnesium-dependent ATPase (Mg2+-ATPase) in rat brains is a target for intravenous anesthetics. The effects of propofol, pentobarbital, and thiopental on magnesium-dependent ATPase in the plasma membrane fraction (PII) and microsomal fraction (PIII) isolated from rat brains homogenates by the method of Pottorf were examined. 　The optimal pH values for Mg2+-ATPase activities in PII and PIII were 9.4 and 7.4, respectively. The Mg2+-ATPase activity of PII was inhibited by about 80% by NaN3 (sodium azide), an inhibitor of F-type ATPase. The Mg2+-ATPase activity of PIII was inhibited by about 30% by the V-type ATPase inhibitor bafilomycin, and by about 10% by the P-type ATPase inhibitor vanadate. Western blotting analysis revealed that the largest amount of F-type ATPase was detected in PII, and the largest amount of V-type ATPase was detected in PIII. We defined all ATPase activity that was insensitive to the above inhibitors as basal Mg2+-ATPase activity. 　In the presence of these inhibitors, we examined the effects of intravenous anesthetics on the activities of various ATPases. Propofol inhibits V-type ATPase activity, PII basal Mg2+-ATPase activity, and PIII basal Mg2+-ATPase activity in a dose-dependent manner; however, F-type ATPase activity was uniquely stimulated about 80% by propofol at concentrations below 0.6 mM. Pentobarbital inhibited all types of ATPases in a dose-dependent manner. Thiopental inhibited all types of ATPases to varying degrees. 　These results suggest that intravenous anesthetics basically inhibit Mg2+-dependent ATPase activities in rat brains, but propofol shows specific effects on mitochondrial ATPase activity.

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