NEUROCHEMICAL ACTIONS OF PSYCHOTROPIC DRUGS

描述（改编自申请人摘要）： 在过去的30年里，这一应用的长期目标是 洗脱大脑中的分子信号系统， 精神药物的作用。我们建议继续描述 多系统，但有三个特殊的foeus：D-丝氨酸，神经元硝酸 氧化物合酶（nNOS）相关蛋白和高级肌醇多磷酸。 (1)D-丝氨酸：我们将扩展D-丝氨酸作为神经调节剂的证据 作为NMDA-谷氨酸受体的内源性配体。我们将 我们最近纯化和克隆的Eharaeeperisine丝氨酸消旋酶， 将L丝氨酸转化为D丝氨酸我们将开发基因敲除和转基因技术， 丝氨酸消旋酶和D-氨基酸氧化酶，这种酶似乎 生理降解D-丝氨酸。(2)nNOS相关蛋白-聚焦CAPON： CAPON是我们发现的一种nNOS相关蛋白，它可能作为一种支架， 将nNOS与其他蛋白质连接。我们最近发现CAPON 与突触蛋白（一种突触囊泡蛋白）和Dexrasl（Ras的新成员） 家人我们将继续研究CAPON作为一个桥梁， nNOS与突触素形成NO，影响突触小血管功能， Dexrasl影响其下游信号传导，从而改变核功能。（三） 高级肌醇多磷酸：高级肌醇多磷酸是 焦磷酸盐，我们认为可能介导 磷酸盐转移到蛋白质，可能与突触囊泡有关 周转我们将继续我们的研究，我们纯化和克隆IP 6 激酶，其形成焦磷酸PP-IP（IP7）。我们将描述 这种酶和一种相关的蛋白质PiUS的功能，PiUS也具有IP 6 激酶活性我们将通过PP-IP表征推定的蛋白质磷酸化 5.我们还将完成PP-IPs激酶的纯化和克隆， 形成含有两个焦磷酸基团的双PP-IP 4

DESCRIPTION(Adapted from applicant's abstract): The long term goal of this application over the past 30 years has been to elueidate molecular signaling systems in the brain whieh may be relevant to aetions of psyehotropic drugs. We propose continuing a characterization of multiple systems but with a special foeus on three: D-serine, neuronal nitric oxide synthase (nNOS) associated proteins, and higher inositol polyphosphates. (1) D-serine: We will extend our evidence for D-serine as a neuromodulator serving as the endogenous ligand for NMDA-glutamate receptors. We will eharaeterize serine racemase, the enzyme we have recently purified and cloned, which converts L- to D-serine. We will develop knockouts and transgenics for serine racemase and d-amino aeid oxidase, the enzyme which appears to physiologically degrade D-serine. (2) nNOS Associated Proteins-Focus on CAPON: CAPON is a nNOS associated protein we discovered, which may serve as a scaffold linking nNOS to other proteins. We recently discovered interactions of CAPON with synapsin, a synaptie vesicle protein, and Dexrasl, a new member of the Ras family. We will continue our studies implicating CAPON as a bridge delivering NO formed by nNOS to synapsin to affect synaptic vesiele funetion, and to Dexrasl to influenee its downstream signaling to alter nuelear funetion. (3) Higher Inositol Polyphosphates: Higher inositol polyphosphates are pyrophosphates with e about :-rgetic phosphate groups that we think may mediate phosphate transfer to proteins, perhaps assoeiated with synaptic vesicle turnover. We will extend our studies in which we purified and cloned IP 6 kinase, which forms the pyrophosphate PP-IPs (IP7 ). We will characterize functions of this enzyme and a related protein, PiUS that also possesses IP6 kinase activity. We will characterize putative protein phosphorylation by PP-IP 5. We will also complete purif aboutcation and cloning of PP-IPs kinase which forms bis PP-IP4, which contains two pyrophosphate groups