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Matsuda T, Shimizu I, Murata Y, Baba A: Glucose and oxygen deprivation induces a Ca (2+)-mediated decrease in (Na (+)+K+)-ATPase activity in rat brain slices. Brain Res. 1992 Apr 3;576(2):263-70. Exposure of rat brain cortical slices to a medium lacking in glucose, oxygen or both glucose and oxygen, resulted in a decrease of the tissue ATP content and a reduction of (Na (+)+K+)-ATPase activity in membranes prepared from the slices. These treatments also inhibited partial reactions of (Na (+)+K+)-ATPase such as Na (+)-dependent phosphorylation and K (+)-stimulated phosphatase, as well as specific binding of [3H] ouabain in membranes prepared from the slices. Glucose deprivation and hypoxia decreased (Na (+)+K+)-ATPase activity in the absence of extracellular Ca2+, but the effects were blocked by 1,2-bis (2-amino-phenoxy) ethane-N,N,N',N'-tetraacetic acid tetra-acetomethyl ester (BAPTA-AM), a chelator of intracellular Ca2+. Metabolic inhibitors mimicked the effects of glucose deprivation and hypoxia. The effect of glucose-free hypoxia was dependent on extracellular Ca2+. It was blocked by Mg2+ at high concentration, bepridil or amiloride, but not by voltage-sensitive Ca2+ channel antagonists and glutamate receptor antagonists. None of the drugs tested here, except for dithiothreitol, affected the inhibitory effect of glucose-free hypoxia on the enzyme activity. In contrast to brain (Na (+)+K+)-ATPase, the kidney enzyme was insensitive to glucose and oxygen deprivation and metabolic inhibitors which depleted the tissue ATP. |
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