title: N-methyl-D-aspartate, kainate and quisqualate release endogenous adenosine from rat cortical slices.
abstract: N-Methyl-D-aspartate, kainate, and quisqualate released endogenous adenosine from superfused slices of rat parietal cortex. N-Methyl-D-aspartate-evoked adenosine release was blocked by D,L-2-amino-5-phosphono-valeric acid and (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK-801), indicating that it was receptor-mediated, although it did not show the expected potentiation in the absence of Mg2+. In contrast, N-methyl-D-aspartate-evoked release of [3H]noradrenaline from the same slices was markedly potentiated in Mg2(+)-free medium. Therefore, the lack of Mg2+ modulation of N-methyl-D-aspartate-evoked adenosine release was not due to depolarization-induced alleviation of the Mg2+ block in the slices. Kainate-evoked adenosine release was diminished by the non-specific excitatory amino acid antagonist, gamma-D-glutamyl-glycine, and kainate- and quisqualate-evoked adenosine release was diminished by 6,7-dinitroquinoxaline-2,3-dione, indicating that these agonists release adenosine by acting at non-N-methyl-D-aspartate receptors. Tetrodotoxin decreased N-methyl-D-aspartate- and kainate-evoked adenosine release by 40% and 19% respectively, indicating that release was mediated in part by propagated action potentials in the slices. Total release of adenosine by N-methyl-D-aspartate, kainate or quisqualate was not diminished in the absence of Ca2+. A second exposure to kainate following restoration of Ca2+ to slices previously depolarized in the absence of Ca2+ resulted in an amount of adenosine release equal to an initial release by slices in the presence of Ca2+, a result suggesting the presence of separate Ca2(+)-dependent and Ca2(+)-independent pools of adenosine. The present experiments demonstrate that activation of all three major subtypes of excitatory amino acid receptors in the cortex releases adenosine, possibly from separate Ca2(+)-dependent and -independent pools. Adenosine released from the cortex following excitatory amino acid stimulation may, by acting at inhibitory P1 purinoceptors, diminish excitatory neurotransmission and protect against excitotoxicity.
authors.affiliation: Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: K
authors.initials: K
authors.lastname: Hoehn
authors.forename: T D
authors.initials: TD
authors.lastname: White
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology*; D004151:Dipeptides / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000494:pharmacology*; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D011810:Quinoxalines / Q000494:pharmacology; D016318:Quisqualic Acid / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D004151:Dipeptides; D011810:Quinoxalines; C028929:gamma-glutamylglycine; D013779:Tetrodotoxin; C056723:FG 9041; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate; D016318:Quisqualic Acid; D008274:Magnesium; D000241:Adenosine; D007608:Kainic Acid; D002118:Calcium; D009638:Norepinephrine