NEUROCHEMICAL ACTIONS OF PSYCHOTROPIC DRUGS

这一应用的长期目标是阐明神经化学 大脑中信号转导系统的各个方面，可能是 精神药物行动的行动。建议进行研究以澄清 肌醇磷脂和一氧化氮信使系统的性质。 肌醇-1，4，5-三磷酸受体蛋白的性质 被刻画出来。磷酸化的生化和功能作用 并将检查受体的糖基化情况。的职能作用 受体的磷酸化和糖基化将通过以下方法进行评估 脂质体中IP3受体蛋白的重组系统 IP3受体的IP3特性选择性刺激钙离子流动 外周组织中的蛋白质将与中央受体进行比较。 肌醇(1，3，4，5)四氢磷酸(IP4)的受体蛋白将是 纯净的。将抗血清发展为IP4受体蛋白，以允许 其免疫组织化学定位。利用纯化的IP4受体 蛋白质重组为脂质体，将努力识别 势能函数，如离子通量的调节。卡尔梅丁，一种膜 大脑中的相关蛋白，它介导钙离子的能力 抑制IP3受体结合，将纯化之间的相互作用 纯化的Calmedin和IP3受体蛋白将在激酶中进行检测， 会产生IP4，将被提纯。纯化酶的抗血清 蛋白质将用于免疫组织化学。 一氧化氮(NO)可能是神经元内的一种信使 大脑中的相互作用。转化率与转化率之间的关系 精氨酸到瓜氨酸和NO的形成将在一个 多种多样的系统。内源性精氨酸池的性质 因为NO的生物合成将通过检测~3H-精氨酸的摄取来探索 以及内源性精氨酸水平的变化。代理人的影响力 影响自由基形成的物质将在NO和环状GMP上进行检测 队形。NO合成的细胞来源将被用来探索 神经学突变小鼠。NO形成酶将被提纯并 提纯抗血清进行免疫组织化学定位。

The long-term goal of this application is to elucidate neurochemical aspects of signal transduction systems in the brain which may be the site of action for psychotropic drug actions. Studies are proposed to clarify properties of the phosphoinositide and nitric oxide messenger systems. Properties of the inositol-1,4,5-triphosphate (IP3) receptor protein will be characterized. The biochemical and functional role of phosphorylation and glycosylation of the receptor will be examined. Functional role of phosphorylation and glycosylation of the receptor will be evaluated through a reconstituted system of the IP3 receptor protein in liposomes whereby calcium flux is stimulated selectively by IP3 Properties of IP3 receptor protein in peripheral tissues will be compared with the central receptor. The receptor protein for inositol (1,3,4,5) tetrakisphosphate (IP4) will be purified. Antisera will be developed to the IP4 receptor protein to permit its immunohistochemical localization. Utilizing the purified IP4 receptor protein reconstituted into liposomes, efforts will be made to identify potential functions ,such as mediation of ion flux. Calmedin, a membrane associated protein in the brain which mediates the ability of calcium to inhibit IP3 receptor binding, will be purified Interactions between purified calmedin and IP3 receptor protein will be examined in kinase, which generates IP4, will be purified. Antisera to the purified enzyme proteins will be employed for immunohistochemistry. Nitric oxide (NO) will be characterized as a possible messenger in neuronal interactions in the brain. The relationship between the conversion of arginine to citrulline and the formation of NO will be examined in a variety of systems. The nature of the endogenous arginine pool employed for NO biosynthesis will be explore by examining the uptake of 3H-arginine and alterations in endogenous arginine levels. The influence of agents that affect free radical formation will be examined on NO and cyclic GMP formation. The cellular source of NO synthesis will be explored utilizing neurologic mutant mice. The NO forming enzyme will be purified and antisera raised for immunohistochemical localization.