title: Amnesic effect of GMP depends on its conversion to guanosine.
abstract: Extracellular guanine-based purines, namely the nucleotides GTP, GDP, GMP and the nucleoside guanosine, exert important neuroprotective and neuromodulator roles in the central nervous system, which may be related to inhibition of the glutamatergic neurotransmission activity. In this study, we investigated GMP effects on mice inhibitory avoidance performance and the dependence on its conversion to guanosine for such effect, by using the ecto-5'-nucleotidase specific inhibitor AOPCP. We also investigated if this conversion occurs in the central nervous system or peripherally, and if guanosine and GMP affect nociception by the tail-flick test. I.p. GMP or guanosine (7.5 mg/kg) or i.c.v. GMP (480 nmol) pretraining administration was amnesic for the inhibitory avoidance task. I.c.v. AOPCP (1 nmol) administration completely reversed the amnesic effect of i.c.v. GMP, but not of i.p. GMP, indicating that peripheral conversion of GMP to guanosine is probably relevant to this effect. AOPCP alone did not interfere with the performance. Furthermore, tail-flick measurement was unaffected by i.p. GMP and guanosine, suggesting that the amnesic effect of both purines was not due to some antinociceptive effect against the footshock used in the task. All these data together, in accordance to those previously observed in studies involving glutamate uptake and seizures reinforce the idea that guanosine is the specific extracellular guanine-based purines effector and indicate that its conversion occurs not only in the central nervous system but also peripherally.
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2600 Anexo CEP 90.035-003, Porto Alegre, RS, Brazil. jonas.saute@ufrgs.br
authors.forename: Jonas Alex Morales
authors.initials: JA
authors.lastname: Saute
authors.forename: Leonardo Evangelista
authors.initials: LE
authors.lastname: da Silveira
authors.forename: Félix Antunes
authors.initials: FA
authors.lastname: Soares
authors.forename: Lúcia Helena
authors.initials: LH
authors.lastname: Martini
authors.forename: Diogo Onofre
authors.initials: DO
authors.lastname: Souza
authors.forename: Marcelo
authors.initials: M
authors.lastname: Ganzella
mesh_terms: D000647:Amnesia / Q000139:chemically induced*; D000818:Animals; D001522:Behavior, Animal; D006151:Guanosine / Q000096:biosynthesis*; D006157:Guanosine Monophosphate / Q000008:administration & dosage / Q000494:pharmacology*; D007262:Infusions, Intravenous; D008297:Male; D008568:Memory / Q000187:drug effects; D051379:Mice; D009619:Nociceptors / Q000187:drug effects
chemical_list: D006151:Guanosine; D006157:Guanosine Monophosphate