Inhibition of Na+, K+-ATPase Activity in Rabbit Kidney by General Anesthetics.
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概要
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Na<SUP>+</SUP>, K<SUP>+</SUP>-ATPase is an enzyme present in all animal cell membranes and plays important roles in various tissues. As it is thought that the inhibition of Na<SUP>+</SUP>, K<SUP>+</SUP>-ATPase by anesthetics and related drugs relates to anesthesia and side effects, the effects of a wide variety of anesthetics and related drugs on the Na<SUP>+</SUP>, K<SUP>+</SUP>-ATPase activity was investigated. Na<SUP>+</SUP>, K<SUP>+</SUP>-ATPase was partially purified from rabbit kidney, and the effects of anesthetics on its activity, the amount of phosphointermediate (EP) and the sensitivity of EP to K<SUP>+</SUP> and ADP were studied. All of the anesthetics except fentanyl inhibited Na<SUP>+</SUP>, K<SUP>+</SUP>-ATPase activity in a dosedependent manner. In volatile anesthetics, a significant correlation was observed between the clinical potency and the concentration that causes half-maximal inhibition (IC<SUB>50</SUB>) of Na<SUP>+</SUP>, K<SUP>+</SUP>-ATPase activity. To study the inhibition mechanism, the sensitivity of Nat, K<SUP>+</SUP>-ATPase and partial reactions of Nat, K<SUP>+</SUP>-ATPase, Na<SUP>+</SUP>-ATPase and K<SUP>+</SUP>-pNPPase activities were compared, to those of anesthetics and related drugs. K<SUP>+</SUP>-pNPPase activity was most sensitive to volatile anesthetics in three activities, whereas K<SUP>+</SUP>-pNPPase activity was most insensitive to benzodiazepines, barbitulates, droperidol and ketamine hydrochloride. Effects of the drugs on EP formation differed among them. Midazoram inhibited EP formation, whereas isoflurane and ketamine hydrochloride did not. The sensitivity of EP to K<SUP>+</SUP> was increased by ketamine hydrochloride but was decreased by isoflurane. These findings suggested that the inhibitory mechanisms of general anesthetics and related drugs against Na<SUP>+</SUP>, K<SUP>+</SUP>-ATPase activity are diverse.
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