title: Extracellular conversion of guanine-based purines to guanosine specifically enhances astrocyte glutamate uptake.
abstract: Guanosine (GUO) has been shown to stimulate glutamate uptake in primary astrocyte cultures. The purpose of this study was to determine the effect and specificity of guanine- or adenine-based purines on glutamate and GABA uptake in cultured astrocytes. Stimulatory effect on glutamate uptake was observed with GUO, GMP or GTP. Simultaneous exposure with these guanine-based purines did not show an additive effect. We also investigated a possible interconversion of guanine-based purines during incubation time. Action by GTP was excluded since the hydrolysis resistant GTP analog, GMP-PNP did not stimulate glutamate uptake. Addition of an ecto-5'-nucleotidase inhibitor abolished GMP-stimulatory effect on glutamate uptake, without affecting GUO action. Taken together, these results suggest that GUO is the guanine-based purines responsible for glutamate uptake activation. In addition, the stimulatory effect on glutamate uptake was not observed with adenine-based purines. Moreover, GABA uptake was not activated by GUO. These results point to specificity in the interaction between GUO and the astrocyte glutamate uptake system.
authors.affiliation: Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 (Anexo), 90035-003 Porto Alegre, RS, Brazil. frizzo@ufrgs.br
authors.forename: Marcos Emílio dos Santos
authors.initials: ME
authors.lastname: Frizzo
authors.forename: Félix Alexandre
authors.initials: FA
authors.lastname: Antunes Soares
authors.forename: Leonara Patrícia
authors.initials: LP
authors.lastname: Dall'Onder
authors.forename: Diogo Rizzato
authors.initials: DR
authors.lastname: Lara
authors.forename: Raymond A
authors.initials: RA
authors.lastname: Swanson
authors.forename: Diogo Onofre
authors.initials: DO
authors.lastname: Souza
mesh_terms: D000244:Adenosine Diphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D006147:Guanine / Q000378:metabolism*; D006151:Guanosine / Q000494:pharmacology*; D006157:Guanosine Monophosphate / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; C523965:alpha,beta-methyleneadenosine 5'-diphosphate; D006151:Guanosine; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D006147:Guanine; D000244:Adenosine Diphosphate; D006157:Guanosine Monophosphate; D006160:Guanosine Triphosphate