title: Blockade of presynaptic adenosine A1 receptor responses by nitric oxide and superoxide in rat hippocampus.
abstract: Activation of N-methyl-D-aspartate (NMDA) receptors prevents the neuronal responses to adenosine in hippocampal slices. As NMDA receptor activation leads to the generation of nitric oxide (NO) and superoxide, we have examined whether these can modify neuronal responses to adenosine and mediate the actions of NMDA. Field excitatory postsynaptic potentials were recorded in the CA1 region of rat hippocampal slices. Paired-pulse interactions were studied to localize the observed interactions to presynaptic terminals. The NO donors S-nitroso-N-acetylpenicillamine and diethylamine NONOate induced a long-lasting potentiation (NO-induced potentiation) of field excitatory postsynaptic potential slope and significantly prevented the presynaptic inhibitory effect of adenosine or the A1 receptor agonist N6-cyclopentyladenosine selectively with no effect on responses to baclofen. The superoxide-generating system of xanthine/xanthine oxidase also prevented presynaptic responses to adenosine and this effect was prevented by superoxide dismutase (SOD). The guanylate cyclase inhibitor 1H-[1,2,4]-oxadiazolo[4,3a]quinoxalin-1-one (10 microM) prevented NO-induced potentiation and the inhibitory effects of S-nitroso-N-acetylpenicillamine and xanthine/xanthine oxidase on adenosine responses. The inhibitory effect of NMDA on adenosine responses was unchanged by 1H-[1,2,4]-oxadiazolo[4,3a]quinoxalin-1-one, indicating that guanosine-3',5-cyclic monophosphate does not mediate this interaction, although it was partially reduced by SOD, suggesting that superoxide might contribute. The reduction of adenosine responses by electrically-induced long-term potentiation was prevented by NO synthase inhibition or SOD. The results indicate that the presynaptic effects of adenosine at presynaptic sites can be prevented by NO or superoxide but that neither of these individually can fully account for the prevention of adenosine responses by NMDA.
authors.affiliation: Institute of Biomedical and Life Sciences, West Medical Building, University of Glasgow, Glasgow G12 8QQ, UK.
authors.forename: Ali
authors.initials: A
authors.lastname: Shahraki
authors.forename: Trevor W
authors.initials: TW
authors.lastname: Stone
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000243:Adenosine Deaminase / Q000494:pharmacology; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000528:radiation effects; D018755:GABA Agonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects; D009569:Nitric Oxide / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D016877:Oxidants / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D013481:Superoxides / Q000494:pharmacology*; D013997:Time Factors; D019820:Xanthine / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018755:GABA Agonists; D020030:Nitric Oxide Donors; D016877:Oxidants; D043682:Receptor, Adenosine A1; C110881:S-nitro-N-acetylpenicillamine; D013481:Superoxides; D019820:Xanthine; D009569:Nitric Oxide; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; D000243:Adenosine Deaminase; D010396:Penicillamine; D001418:Baclofen; D000241:Adenosine