title: Adenosine A1 receptor activation modulates N-methyl-d-aspartate (NMDA) preconditioning phenotype in the brain.
abstract: N-methyl-d-aspartate (NMDA) preconditioning is induced by subtoxic doses of NMDA and it promotes a transient state of resistance against subsequent lethal insults. Interestingly, this mechanism of neuroprotection depends on adenosine A1 receptors (A1R), since blockade of A1R precludes this phenomenon. In this study we evaluated the consequences of NMDA preconditioning on the hippocampal A1R biology (i.e. expression, binding properties and functionality). Accordingly, we measured A1R expression in NMDA preconditioned mice (75mg/kg, i.p.; 24h) and showed that neither the total amount of receptor, nor the A1R levels in the synaptic fraction was altered. In addition, the A1R binding affinity to the antagonist [(3)H] DPCPX was slightly increased in total membrane extracts of hippocampus from preconditioned mice. Next, we evaluated the impact of NMDA preconditioning on A1R functioning by measuring the A1R-mediated regulation of glutamate uptake into hippocampal slices and on behavioral responses in the open field and hot plate tests. NMDA preconditioning increased glutamate uptake into hippocampal slices without altering the expression of glutamate transporter GLT-1. Interestingly, NMDA preconditioning also induced antinociception in the hot plate test and both effects were reversed by post-activation of A1R with the agonist CCPA (0.2mg/kg, i.p.). NMDA preconditioning or A1R modulation did not alter locomotor activity in the open field. Overall, the results described herein provide new evidence that post-activation of A1R modulates NMDA preconditioning-mediated responses, pointing to the importance of the cross-talk between glutamatergic and adenosinergic systems to neuroprotection.
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, UFSC, Campus Trindade, 88040-900 Florianópolis, SC, Brazil.
authors.forename: Leandra C
authors.initials: LC
authors.lastname: Constantino
authors.affiliation: D'Or Institute for Research and Education (IDOR), Rio de Janeiro, RJ, Brazil.
authors.forename: Fabrício A
authors.initials: FA
authors.lastname: Pamplona
authors.affiliation: Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, UFSC, Campus Trindade, 88040-900 Florianópolis, SC, Brazil.
authors.forename: Filipe C
authors.initials: FC
authors.lastname: Matheus
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, UFSC, Campus Trindade, 88040-900 Florianópolis, SC, Brazil; Curso de Farmácia, Universidade do Contestado - UnC, 89460-000 Canoinhas, SC, Brazil.
authors.forename: Fabiana K
authors.initials: FK
authors.lastname: Ludka
authors.affiliation: Unitat de Farmacologia, Departament de Patologia i Terapèutica Experimental, Facultat de Medicina, IDIBELL-Universitat de Barcelona, L'Hospitalet de Llobregat, 08907 Barcelona, Spain.
authors.forename: Maricel
authors.initials: M
authors.lastname: Gomez-Soler
authors.affiliation: Unitat de Farmacologia, Departament de Patologia i Terapèutica Experimental, Facultat de Medicina, IDIBELL-Universitat de Barcelona, L'Hospitalet de Llobregat, 08907 Barcelona, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Ciruela
authors.affiliation: Programa de Pós-graduação em Nanociências, Centro Universitário Franciscano, Santa Maria, RS, Brazil.
authors.forename: Carina R
authors.initials: CR
authors.lastname: Boeck
authors.affiliation: Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, UFSC, Campus Trindade, 88040-900 Florianópolis, SC, Brazil.
authors.forename: Rui D
authors.initials: RD
authors.lastname: Prediger
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, UFSC, Campus Trindade, 88040-900 Florianópolis, SC, Brazil. Electronic address: carla.tasca@ufsc.br.
authors.forename: Carla I
authors.initials: CI
authors.lastname: Tasca
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D058916:Adenosine A1 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects; D016202:N-Methylaspartate / Q000494:pharmacology*; D058906:Purinergic P1 Receptor Agonists / Q000494:pharmacology; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D014970:Xanthines / Q000494:pharmacology
chemical_list: D058916:Adenosine A1 Receptor Antagonists; D018690:Excitatory Amino Acid Agonists; D027342:Excitatory Amino Acid Transporter 2; D058906:Purinergic P1 Receptor Agonists; D043682:Receptor, Adenosine A1; D014970:Xanthines; C058394:2-chloro-N(6)cyclopentyladenosine; D018698:Glutamic Acid; D016202:N-Methylaspartate; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine
keywords: Adenosine A(1) receptors; Glutamate; Hippocampus; NMDA preconditioning; Pain