Extracellular conversion of guanine-based purines to guanosine specifically enhances astrocyte glutamate uptake.
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.
Frizzo
Marcos Emílio dos Santos
ME
Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 (Anexo), 90035-003 Porto Alegre, RS, Brazil. frizzo@ufrgs.br
Antunes Soares
Félix Alexandre
FA
Dall'Onder
Leonara Patrícia
LP
Lara
Diogo Rizzato
DR
Swanson
Raymond A
RA
Souza
Diogo Onofre
DO
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
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