CELL MEMBRANE ACTIVITY IN FUNCTIONAL PSYCHOSES

功能性精神病中的细胞膜活动

• 批准号: 3374978
• 负责人: MABEL R HOKIN
• 金额: $ 11.39万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-08-15 至 1988-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3374978
• 关键词: adenosinetriphosphatase; cell membrane; erythrocyte membrane; human subject; lithium; membrane permeability; mental disorder chemotherapy; mental disorder diagnosis; ouabain; phosphatidylcholines; phosphatidylethanolamines; phosphatidylinositols; phosphatidylserines; psychobiology; psychopharmacology; radiotracer; schizophrenia

Overall objectives are to study membrane NaK-ATPase activity and endogenous ouabain-like regulatory factors in bipolar affective disorder, and to study the effects of lithium therapy on phosphoinositide metabolism. A major aim is to determine whether there is a variant of the NaK-ATPase which is specific for bipolar affective disorder. Radioactive photoaffinity labels will be developed which will label both the alpha and beta subunits of the enzyme in erythrocyte membranes and in post mortem brain tissue. Methods will be developed for the separation of the labeled enzyme subunits and selective degradation products. These will be used to determine whether a variant form of the enzyme can be demonstrated in bipolar affective disorder. If successful, an attempt will be made to develop a diagnostic test for the disorder, based on these findings. A second aim is to investigate whether there may be abnormal regulation of NaK-ATPase activity by an endogenous ouabain-like factor in bipolar affective disorder. Factors which inhibit NaK-ATPase activity and displace ouabain-binding will be isolated from animal brain and other tissues. These will be tested against erythrocyte NaK-ATPase from bipolar and normal subjects to determine whether there is any difference in affinity or extend of inhibitory activity. Possible changes in affinity or susceptibility to inhibition by these factors during lithium therapy will be followed. Methodology will be developed for the assay of circulating ouabain-like inhibitory factor in extracts of blood plasma. Circulating levels of inhibitory factor will be measured in normal and bipolar subjects, and during lithium therapy. A third aim is to determine whether the responsivity of the membrane phosphoinositide signal system changes during lithium therapy. Responses which involve the phophoinositide signal system will be measured in platelets from patients receiving lithium therapy and compared with responses before lithium therapy and in normal controls. The levels of inosito, inositol phosphates, phosphoinositides and other lipids will be measured in lymphocytes, platelets and erythrocytes from patients receiving lithium therapy and will be compared with the levels in normal controls.

总体目标是研究膜NaK-ATP酶活性和内源性 双相情感障碍中哇巴因样调节因子的研究 锂治疗对磷酸肌醇代谢的影响。 一个主要的目的是确定是否有一个变异的钠钾ATP酶 这是双相情感障碍特有的 放射性 将开发光亲和标记，其将标记α和 β亚单位的酶在红细胞膜和死后 脑组织 将开发用于分离标记的 酶亚基和选择性降解产物。 这些将用于 确定酶的变体形式是否可以在 双相情感障碍 如果成功，将尝试 根据这些发现，开发一种针对这种疾病的诊断测试。 第二个目的是调查是否存在异常调节， 内源性哇巴因样因子介导的双极细胞Na K-ATP酶活性 情感障碍 抑制NaK-ATP酶活性和置换 哇巴因结合物将从动物脑和其它组织中分离。 这些将针对来自双极和正常的红细胞NaK-ATP酶进行测试。 受试者，以确定是否有任何差异，在亲和力或延伸 抑制活性。 可能的亲和力或易感性变化 将跟踪锂治疗期间这些因子的抑制。 将开发用于测定循环哇巴因样 血浆提取物中的抑制因子。 循环水平 将在正常和双相受试者中测量抑制因子， 在锂治疗期间。 第三个目标是确定膜的响应度是否 磷酸肌醇信号系统在锂治疗期间改变。 响应 涉及磷酸肌醇信号系统将在 接受锂治疗的患者的血小板，并与 锂治疗前和正常对照组的反应。 水平 肌醇、磷酸肌醇、磷酸肌醇和其它脂质将被 在接受以下治疗的患者的淋巴细胞、血小板和红细胞中测量： 锂治疗，并将与正常对照组的水平进行比较。