Mechanism for propofol inhibition of Na＋, K＋-ATPase activity in rat brain
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概要
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Propofol is one of the most widely used intravenous anesthetics, however the mechanism of the anesthetic effect is not fully understood. Na+,K+-ATPase is an enzyme present in all animal cell membranes and plays essential roles for the maintenance of neuronal excitability. There is a report of propofol inhibition of Na+,K+-ATPase activity, but the mechanism is not clearly established. To study the mechanism for propofol inhibition of Na+,K+-ATPase purified from whole brains of rats, the effects of propofol on Na+,K+-ATPase activity, Na+-ATPase, and K+-pNPPase activities, which are partial reactions of Na+,K+-ATPase were examined. Na+,K+-ATPase and Na+-ATPase activities decreased depending on the concentration of propofol, and were completely inhibited at 1.03 mM. Propofol decreased the maximum activity of Na+-, K+-, Mg2+-, and ATPdependent activation of Na+,K+-ATPase activity depending on its concentration, and changed the half maximal concentration for Na+, K+, and ATP, but not for Mg2+. Propofol also decreased the maximum activities of Na+-ATPase and K+-pNPPase, suggesting that propofol inhibits Na+,K+-ATPase activity by affecting the whole reaction process of Na+,K+-ATPase. The inhibition of Na+,K+-ATPase activity by propofol was reversible by dilution of its concentration. These results suggest that propofol reversibly inhibits Na+,K+-ATPase activity in a mixed-type inhibition pattern.
著者
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Suzuki Kuniaki
Department Of Dental Pharmacology School Of Dentistry Hokkaido University
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Suzuki Kuniaki
Department Of Oral Pathobiological Science Graduate School Of Dental Medicine Hokkaido University
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Suzuki K
Department Of Chemistry Faculty Of Science Kanazawa University
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Yoshimura Yoshitaka
Department Of Oral Pathobiological Science Graduate School Of Dental Medicine Hokkaido University
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