Neurochemical Actions of Psychotropic Drugs

Johns Hopkins University, Baltimore MD

Investigators

Linked publications & trials

Abstract

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