CELL MEMBRANE ACTIVITY IN FUNCTIONAL PSYCHOSES

总体目标是研究膜NAK-ATPase活性和内源 哇巴因样调节因子在双相情感障碍中的研究 锂治疗对肌醇磷脂代谢的影响。 主要目的是确定是否存在NAK-ATPase的变体 这是双相情感障碍所特有的。放射性 将开发光亲和标签，它将标记阿尔法和 红细胞膜和身体中酶的β亚基 脑组织。将开发分离标记的方法 酶亚基和选择性降解产物。这些将被用来 确定该酶的变种形式是否可以在 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。 第二个目标是调查是否存在不正常的监管 双相患者内源性哇巴因样因子对NAK-ATPase活性的影响 情感障碍。抑制NAK-ATPase活性和置换的因素 哇巴因结合将从动物的大脑和其他组织中分离出来。 这些将与来自双相和正常的红细胞NAK-ATPase进行测试 受试者要确定在亲和力或广度上是否有任何差异 具有抑制活性。亲和力或易感性的可能变化 在锂治疗期间，这些因素的抑制将随之而来。 将建立循环中哇巴因样物的检测方法 血浆提取物中的抑制因子。循环中的水平 抑制因子将在正常和双相受试者中进行测量，并且 在锂治疗期间。 第三个目标是确定膜的响应性 锂治疗过程中磷脂酰肌醇信号系统的变化。回应 其中涉及磷脂酰肌醇的信号系统将在 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。的水平 肌醇、肌醇磷酸盐、肌醇磷脂和其他脂类 从患者的淋巴细胞、血小板和红细胞中检测 锂治疗，并将与正常对照组的水平进行比较。

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.