SODIUM POTASSIUM ATPASE--FUNCTION AND REGULATION, ALCOHOLISM, NEUROSCIENCE

质膜Na~+，K~+-ATPase的抑制 有充分的证据表明，活动通过以下方式促进神经元退化 增强神经元对谷氨酸诱导的敏感性 兴奋性毒性。弗利博士发现，在某些特定的定义下 条件下，低浓度(毫摩尔)的乙醇抑制 突触体膜Na~+，K~+-ATPase活性途径 继发于环氧合酶(COX)活性的激活。在……里面 此外，他还证明了COX过氧化氢 产物PGG2可有效抑制Na+，K+-ATPase活性 明显的过氧化氢依赖机制，不涉及 前列腺素或氧自由基的形成。他向我求婚了 PGG2对Na+，K+-ATPase活性的抑制可能是一种 在条件下导致神经元毒性的常见机制， 例如乙醇的存在，促进了COX的增加 活动。正在进行的工作旨在建立准确的 苦参碱抑制Na~+，K~+-ATPase活性的生化基础 PGG2。注：此前，该项目的首席调查员 马尔库·林诺伊拉，医学博士，1998年2月去世。 在本报告所述期间进行的研究 蒂莫西·福利博士写的。

Inhibition of plasma membrane Na+, K+-ATPase activity is well documented to promote neuronal degeneration by enhancing the sensitivity of neurons to glutamate induced excitotoxicity. Dr. Foley has found that, under certain defined conditions, low (millimolar) concentrations of ethanol inhibited synptosomal membrane Na+, K+-ATPase activity by a pathway that was secondary to activation of cyclooxygenase (COX) activity. In addition, he has demonstrated that the COX hydroperoxide product, PGG2, potently inhibited Na+, K+-ATPase activity by an apparent hydroperoxide-dependent mechanism that did not involve formation of prostaglandins or oxygen radicals. He has proposed that inhibition of Na+, K+-ATPase activity by PGG2 may be a common mechanism leading to neuronal toxicity under conditions, such as the presence of ethanol, that promote increases in COX activity. Ongoing work is aimed at establishing the exact biochemical basis for the inhibition of Na+, K+-ATPase activity by PGG2. NOTE: Previously, the Principal Investigator of this project was Markku Linnoila, M.D., Ph.D., who died in February, 1998. The research conducted during this reporting period was performed by Dr. Timothy Foley.