Inhibition of Na, K-ATPase activity by local anesthetics in rabbit brain and kidney and rat brain.

概要

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It was assumed that local anesthetics might act on proteins nonspecifically and that the effects of local anesthesia might be the result of such actions. Using Na, K-ATPase as a model, the effects of lidocaine, procaine, and dibucaine on Na, K-ATPase activity was studied to test our hypothesis. Na, K-ATPase from rabbit brain and kidney and rat brain was partially purified and Na, K-ATPase activity was determined by measurement of inorganic phosphate production by Chifflet's method. Lidocaine, procaine, and dibucaine inhibited all Na, K-ATPase activities, depending on their concentrations. The inhibition by lidocaine was complete at the concentration for its clinical usage. IC50 values, which are the concentrations to give the half maximal inhibition, were determined for each anesthetic and the enzyme. The anesthetic with strong local anesthetic action and toxicity gave a smaller IC50 value. The IC50 values of each anesthetic for rabbit brain and kidney and rat brain were similar. As the concentration-dependent inhibition curves were sigmoidal, they were analyzed by the Hill plot. The Hill coefficients of all the anesthetics and the enzymes were around 0.4 to 0.6, suggesting negative cooperation between the binding sites for local anesthetics. These results support our hypothesis mentioned above.
日本歯科薬物療法学会の論文