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Neurochemical Actions of Psychotropic Drugs

精神药物的神经化学作用

基本信息

批准号：
7417480
负责人：
SOLOMON H. SNYDER
金额：
$ 119.36万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1985
资助国家：
美国
起止时间：
1985-09-01 至 2010-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7417480
关键词：
ADP ribosylation Affect Amino Acid Sequence Amino Acids Area Aspartate Astrocytes Binding Binding Sites Biological Process Brain Calcium Channel Cell Line Cell physiology Cloning Complementary DNA Consensus D-Amino Acid Dehydrogenase Databases Diphosphates Enzymes Family GTP-Binding Proteins Glutamate Receptor Glutamates Glycine Goals Grant Hybrids Immunohistochemistry In Situ Hybridization Inositol Inositol Phosphates Interstitial Cell of Cajal Intestines Kidney Knock-out Knockout Mice Ligands Link Liver Localized Long-Term Potentiation Mediating Mitogen-Activated Protein Kinases Molecular Mus Mutagenesis N-Methyl-D-Aspartate Receptors N-Methylaspartate N-terminal NOS1 protein, human Neuromodulator Neurons Neurotransmitters Nitric Oxide Nitric Oxide Donors Nitric Oxide Synthase Nitric Oxide Synthase Type I Nuclear Numbers Oxidases PTB Domain Peripheral Peripheral Nervous System Pharmaceutical Preparations Phosphorylation Phosphorylation Site Phosphotransferases Physiological Play Polyphosphates Population Potassium Progress Reports Property Protein Overexpression Proteins Psychotropic Drugs Pyridoxal Phosphate Role Route Serine Signal Transduction Site Staining method Stains Structure Sulfhydryl Compounds Synapses Synapsins Synaptic Vesicles System Techniques Thinking Tissues Transgenic Mice Transgenic Organisms Vesicle Work Yeasts abstracting base brain tissue cell motility citrate carrier comparative granule cell gray matter human TYRP1 protein inorganic phosphate inositol hexakisphosphate kinase interest interstitial cell knockout gene member neurochemistry neurotransmission protein 4.1 ras Proteins receptor research study scaffold serine racemase transmission process uptake

项目摘要

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.

描述（改编自申请人摘要）：