title: Enhanced adenosine A2A receptor facilitation of synaptic transmission in the hippocampus of aged rats.
abstract: Adenosine either inhibits or facilitates synaptic transmission through A1 or A2A receptors, respectively. Since A2A receptor density increases in the limbic cortex of aged (24 mo) compared with young adult rats (2 mo), we tested if A2A receptor modulation of synaptic transmission was also increased in aged rats. The A2A receptor agonist, CGS21680 (10 nM), caused a larger facilitation of the field excitatory postsynaptic potential (fEPSP) slope in hippocampal slices of aged (38%) than in young rats (19%), an effect prevented by the A2A receptor antagonist, ZM241385 (20 nM). In contrast to young rats, where CGS21680 facilitation of fEPSPs is prevented by the protein kinase C inhibitor, chelerythrine (6 microM), but not by the protein kinase A inhibitor, H-89 (1 microM), the CGS21680-induced facilitation of fEPSP slope in aged rats was prevented by H-89 (1 microM) but not by chelerythrine (6 microM). Also, in contrast to the beta-receptor agonist, isoproterenol (30 microM), CGS21680 (100-1,000 nM) enhanced cAMP levels in hippocampal nerve terminals of aged but not young rats. Finally, we observed a significant increase of both the binding density of [3H]CGS 21680 and the [3H]ZM241385 as well as of the anti-A2A receptor immunoreactivity in hippocampal nerve terminal membranes from aged compared with young rats. This shows that A2A receptor-mediated facilitation of hippocampal synaptic transmission is larger in aged than young rats due to increased A2A receptor density in nerve terminals and to the modified transducing system operated by A2A receptors, from a protein kinase C mediated control of A1 receptors into a direct protein kinase A dependent facilitation of synaptic transmission.
authors.affiliation: Center for Neurosciences of Coimbra, Institute of Biochemistry, Faculty of Medicine, University of Coimbra, Portugal.
authors.forename: Nelson
authors.initials: N
authors.lastname: Rebola
authors.forename: Ana M
authors.initials: AM
authors.lastname: Sebastião
authors.forename: Alexandre
authors.initials: A
authors.lastname: de Mendonca
authors.forename: Catarina R
authors.initials: CR
authors.lastname: Oliveira
authors.forename: J A
authors.initials: JA
authors.lastname: Ribeiro
authors.forename: Rodrigo A
authors.initials: RA
authors.lastname: Cunha
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000375:Aging / Q000502:physiology*; D000818:Animals; D015153:Blotting, Western; D000242:Cyclic AMP / Q000378:metabolism; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010627:Phenethylamines / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000737:chemistry*; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1 / Q000032:analysis / Q000502:physiology*; D009435:Synaptic Transmission; D014227:Triazines / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
chemical_list: D000318:Adrenergic beta-Agonists; D010627:Phenethylamines; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1; D014227:Triazines; D014230:Triazoles; D014970:Xanthines; C097270:ZM 241385; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000242:Cyclic AMP; D000241:Adenosine; D007545:Isoproterenol