Effects of adenosine A₁ and A_2A receptor activation on the evoked release of glutamate from rat cerebrocortical synaptosomes

<jats:p> <jats:list list-type="explicit-label"> <jats:list-item><jats:p>The effects of adenosine A<jats:sub>2A</jats:sub> and A<jats:sub>1</jats:sub> receptor activation on the release of glutamate were studied in rat cerebral cortex synaptosomes exposed in superfusion to adenosine receptor ligands.</jats:p></jats:list-item> <jats:list-item><jats:p>Adenosine (0.1 μ<jats:sc>M</jats:sc>) produced a significant potentiation of the Ca<jats:sup>2+</jats:sup>‐dependent K<jats:sup>+</jats:sup>(15 m<jats:sc>M</jats:sc>)‐evoked [<jats:sup>3</jats:sup>H]‐<jats:sc>D</jats:sc>‐aspartate overflow (20.4±3.5%), which was blocked by A<jats:sub>2A</jats:sub> blocker SCH58261 (0.1 μ<jats:sc>M</jats:sc>). At higher concentrations (10 – 1000 μ<jats:sc>M</jats:sc>) adenosine inhibited in a DPCPX‐sensitive manner the Ca<jats:sup>2+</jats:sup>‐dependent K<jats:sup>+</jats:sup>‐evoked [<jats:sup>3</jats:sup>H]‐<jats:sc>D</jats:sc>‐aspartate overflow. The inhibitory effect of adenosine at 1000 μ<jats:sc>M</jats:sc> was significantly increased by SCH58261. This inhibition was antagonized by 1 μ<jats:sc>M</jats:sc> DPCPX. Adenosine did not produce any effect on basal release.</jats:p></jats:list-item> <jats:list-item><jats:p>The A<jats:sub>2A</jats:sub> receptor agonist CGS 21680 was ineffective on basal release, but stimulated the Ca<jats:sup>2+</jats:sup>‐dependent K<jats:sup>+</jats:sup>‐evoked overflow of [<jats:sup>3</jats:sup>H]‐<jats:sc>D</jats:sc>‐aspartate (EC<jats:sub>50</jats:sub> ≃ 1 p<jats:sc>M</jats:sc>). The effect of 0.01 n<jats:sc>M</jats:sc> CGS 21680 was totally sensitive to the A<jats:sub>2A</jats:sub> receptor antagonist SCH58261 (IC<jats:sub>50</jats:sub> ≃5 n<jats:sc>M</jats:sc>).</jats:p></jats:list-item> <jats:list-item><jats:p>The A<jats:sub>1</jats:sub> receptor agonist CCPA inhibited the Ca<jats:sup>2+</jats:sup>‐dependent K<jats:sup>+</jats:sup>‐evoked [<jats:sup>3</jats:sup>H]‐<jats:sc>D</jats:sc>‐aspartate overflow (EC<jats:sub>50</jats:sub> ≃ 20 n<jats:sc>M</jats:sc>). The effect of 100 n<jats:sc>M</jats:sc> CCPA was abolished by 100 n<jats:sc>M</jats:sc> of the A<jats:sub>1</jats:sub> receptor antagonist DPCPX.</jats:p></jats:list-item> <jats:list-item><jats:p>The K<jats:sup>+</jats:sup>(15 m<jats:sc>M</jats:sc>)‐evoked overflow of endogenous glutamate was enhanced by CGS 21680 (0.01 n<jats:sc>M</jats:sc>) and inhibited by CCPA (0.1 μ<jats:sc>M</jats:sc>). The effect of CGS 21680 was abolished by SCH58261 (0.1 μ<jats:sc>M</jats:sc>) and that of CCPA by DPCPX (0.1 μ<jats:sc>M</jats:sc>).</jats:p></jats:list-item> <jats:list-item><jats:p>It is concluded that adenosine and adenosine receptor agonists modulate glutamate release by activating inhibitory A<jats:sub>1</jats:sub> and excitatory A<jats:sub>2A</jats:sub> receptors present on glutamatergic terminals of the rat cerebral cortex.</jats:p></jats:list-item> </jats:list> </jats:p><jats:p><jats:italic>British Journal of Pharmacology</jats:italic> (2002) <jats:bold>136</jats:bold>, 434–440; doi:<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" xlink:href="10.1038/sj.bjp.0704712">10.1038/sj.bjp.0704712</jats:ext-link></jats:p>