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N ‐Methyl‐ d ‐Aspartate‐ and Non‐ N ‐Methyl‐ d ‐Aspartate‐Evoked Adenosine Release from Rat Cortical Slices: Distinct Purinergic Sources and Mechanisms of Release
Author(s) -
Craig Constance G.,
White Thomas D.
Publication year - 1993
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1993.tb03256.x
Subject(s) - kainate receptor , nmda receptor , adenosine , ampa receptor , chemistry , glutamate receptor , purinergic receptor , adenosine receptor , inhibitory postsynaptic potential , ionotropic effect , adenosine a1 receptor , pharmacology , biochemistry , biology , neuroscience , receptor , agonist
Excitatory amino acids, acting at both N methyl‐ d ‐aspartate (NMDA) and non‐NMDA receptors, release the inhibitory neuromodulator adenosine from superfused rat cortical slices. This study was initiated to investigate the possible purinergic sources and mechanisms of release for the adenosine release evoked by NMDA and non‐NMDA receptor activation. Inhibition of the bidirectional nucleo‐side transporter with dipyridamole greatly enhanced adenosine release evoked by glutamate, NMDA, kainate, and ( RS ‐α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA). Inhibition of ecto ‐5′‐nucleotidase with α,β‐methylene ADP and GMP had no effect on either kainateor AMPA‐evoked adenosine release, but it decreased glutamate‐ and NMDA‐evoked adenosine release by 23 and 68%, respectively. A similar inhibition of NMDA‐evoked adenosine release was observed with α,β‐methylene ADP alone, indicating that the inhibitory effect was not due to the reported competitive inhibition of NMDA receptors by GMP. Finally, NMDA‐evoked adenosine release, but not kainate‐ or AMPA‐evoked release, was Ca 2+ dependent. These results indicate that activation of non‐NMDA receptors releases adenosine per se in a Ca 2+ ‐independent manner. In contrast, NMDA receptor activation releases primarily a nucleotide that is subsequently converted extracellularly to adenosine; in this case, release is Ca 2+ dependent. Although neither NMDA‐ nor non‐NMDA‐evoked adenosine release occurs via the nucleoside transporter, this transporter does appear to be a major route for removal of adenosine from the extracellular space.