Release of endogenous adenosine and its metabolites by the activation of NMDA receptors in the rat hippocampus in vivo

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Abstract
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 μm during the first 2 h after the implantation of the dialysis probe. NMDA (50 μm to 25 mm) in the perfusate evoked a concentration-dependent release of adenosine, inosine and hypoxanthine with an EC50 of 180 μm. The release was reduced by 93% by the specific NMDA receptor antagonist 2-amino-5-phosphonopentanoic acid (2-AP5) at 200 μm, indicating an NMDA receptor-mediated process. In addition, the 100 mm 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-Ca2+ 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.