title: Cross talk between A(1) and A(2A) adenosine receptors in the hippocampus and cortex of young adult and old rats.
abstract: Adenosine modulates synaptic transmission by acting on inhibitory A(1) and facilitatory A(2A) receptors, the densities of which are modified in aged animals. We investigated how A(2A) receptor activation influences A(1) receptor function and whether this interaction is modified in aged rats. In hippocampal and cortical nerve terminals from young adult (6 wk), but not old rats (24 mo), the A(2A) receptor agonist, 2-[4-(2-carboxyethyl) phenethylamino]-5'-N-ethylcarboxamidoadenosine (CGS 21680; 30 nM) decreased the binding affinity of a selective A(1) receptor agonist, cyclopentyladenosine (CPA), an effect prevented by the A(2A) antagonist, (4-(2-[7-amino-2-(2-furyl (1,2,4)-triazolo(2,3-a (1,3,5)triazin-5-yl-aminoethyl)phenol (ZM 241385, 20 nM). This effect of CGS 21680 required intact nerve terminals and was also observed in the absence of Ca(2+). This A(2A)-induced "desensitization" of A(1) receptors was prevented by the protein kinase C inhibitor, chelerythrine (6 microM), and was not detected in the presence of the protein kinase C activator, phorbol-12,13-didecanoate (250 nM), which itself caused a reduction in binding affinity for CPA. The protein kinase A inhibitor, N-(2-guanidinoethyl)-5-isoquinolinesulfonamide (10 microM), and the protein kinase A activator, 8-Br-cAMP (1 mM), had no effects on the A(2A)-induced A(1) receptor desensitization. This A(2A)-induced A(1) receptor desensitization had a functional correlation because CGS 21680 (10 nM) attenuated by 40% the inhibition caused by CPA (10 nM) on CA1 area population spike amplitude in hippocampal slices. This A(2A)/A(1) interaction may explain the attenuation by adenosine deaminase (2 U/ml), which removes tonic A(1) inhibition, of the facilitatory effect of CGS 21680 on synaptic transmission. The requirement of tonic A(1) receptor activation for CGS 21680 to induce facilitation of synaptic transmission was reinforced by the observation that the A(1) receptor antagonist, 1, 3-dipropyl-8-cyclopentylxanthine (20 nM) prevented CGS 21680 (10 nM) facilitation of population spike amplitude. The present results show the ability of A(2A) receptors to control A(1) receptor function in a manner mediated by protein kinase C, but not protein kinase A, in young adult but not in aged rats.
authors.affiliation: Laboratory of Neurosciences, Faculty of Medicine, University of Lisbon, 1649-028 Lisbon, Portugal.
authors.forename: L V
authors.initials: LV
authors.lastname: Lopes
authors.forename: R A
authors.initials: RA
authors.lastname: Cunha
authors.forename: J A
authors.initials: JA
authors.lastname: Ribeiro
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000375:Aging / Q000502:physiology*; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D004594:Electrophysiology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D010627:Phenethylamines / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D020239:Receptor Cross-Talk / Q000187:drug effects / Q000502:physiology*; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D013570:Synaptic Membranes / Q000187:drug effects; D014227:Triazines / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
chemical_list: 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; D015124:8-Bromo Cyclic Adenosine Monophosphate; C048599:N(6)-cyclopentyladenosine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D011493:Protein Kinase C; D000241:Adenosine