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Neurochemical Characterization of a Neuroprotective Compound from Parawixia bistriata Spider Venom That Inhibits Synaptosomal Uptake of GABA and Glycine

Department of Biochemistry and Immunology, Ribeirão Preto School of Medicine, University of São Paulo, São Paulo, Brazil (R.O.B., R.O.G.C., J.C.-N.); Department of Biology, Ribeirão Preto Faculty of Philosophy, Sciences, and Literature, University of São Paulo, São Paulo, Brazil (R.G., A.B.P., W.F.d.S.); Department of Physics and Chemistry, Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, São Paulo, Brazil (L.G.-N, N.P.L.); Department of Neurobiology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania (A.C.K.F.); and Department of Biotechnology, University of Ribeirão Preto, São Paulo, Brazil (R.O.B.)

The major contribution of this work is the isolation of a neuroprotective compound referred to as 2-amino-5-ureidopentanamide (FrPbAII) (M_r = 174) from Parawixia bistriata spider venom and an investigation of its mode of action. FrPbAII inhibits synaptosomal GABA uptake in a dose-dependent manner and probably does not act on Na⁺, K⁺, and Ca²⁺ channels, GABA_B receptors, or -aminobutyrate:-ketoglutarate aminotransferase enzyme; therefore, it is not directly dependent on these structures for its action. Direct increase of GABA release and reverse transport are also ruled out as mechanisms of FrPbAII activities as well as unspecific actions on pore membrane formation. Moreover, FrPbAII is selective for GABA and glycine transporters, having slight or no effect on monoamines or glutamate transporters. According to our experimental glaucoma data in rat retina, FrPbAII is able to cross the blood-retina barrier and promote effective protection of retinal layers submitted to ischemic conditions. These studies are of relevance by providing a better understanding of neurochemical mechanisms involved in brain function and for possible development of new neuropharmacological and therapeutic tools.

Received for publication August 22, 2005.

Accepted for publication March 21, 2006.

Address correspondence to: Dr. Wagner F. dos Santos, Department of Biology, Faculty of Philosophy, Sciences, and Literature, University of São Paulo, Av. Bandeirantes, 3900-Ribeirão Preto, São Paulo, Brazil, 14040-901. E-mail: wagnerf{at}usp.br

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