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Release of endogenous adenosine and its metabolites by the activation of NMDA receptors in the rat hippocampus in vivo
Author(s) -
Chen Ying,
Graham D.I.,
Stone T.W.
Publication year - 1992
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1992.tb14387.x
Subject(s) - nmda receptor , microdialysis , adenosine , inosine , hypoxanthine , chemistry , veratridine , glutamate receptor , adenosine a1 receptor , agonist , receptor , pharmacology , medicine , endocrinology , biochemistry , adenosine receptor , biology , extracellular , organic chemistry , sodium channel , enzyme , sodium
1 The effects of N‐methyl‐ d ‐aspartate (NMDA), KCl, and veratridine on the release of endogenous adenosine and its metabolites, inosine and hypoxanthine, from the rat hippocampus have been studied by in vivo microdialysis. 2 In the hippocampus of rats anaesthetized with urethane the adenosine level reached a stable state estimated at 0.93 μ m during the first 2 h after the implantation of the dialysis probe. NMDA (50 μ m to 25 m m ) in the perfusate evoked a concentration‐dependent release of adenosine, inosine and hypoxanthine with an EC 50 of 180 μ m . The release was reduced by 93% by the specific NMDA receptor antagonist 2‐amino‐5‐phosphonopentanoic acid (2‐AP5) at 200 μ m , indicating an NMDA receptor‐mediated process. In addition, the 100 m m KCl‐evoked release of adenosine was also substantially reduced by 77% by 2‐AP5, suggesting that a large component of the K + ‐evoked release is NMDA‐receptor‐mediated. 3 Perfusion with zero‐Ca 2+ artificial cerebrospinal fluid attenuated the NMDA‐evoked release of adenosine only by 16% (not signficant) but depressed the K + ‐evoked release by 62%, indicating that most of the NMDA‐evoked release is directly receptor‐mediated, whereas a large component of the K + ‐evoked release could be via the release of an excitatory amino acid acting at the NMDA receptors.