Effects of adenosine A1 and A2A receptor activation on the evoked release of glutamate from rat cerebrocortical synaptosomes

1 The effects of adenosine A(2A) and A(1) receptor activation on the release of glutamate were studied in rat cerebral cortex synaptosomes exposed in superfusion to adenosine receptor ligands. 2 Adenosine (0.1 muM) produced a significant potentiation of the Ca2+-dependent K+(15 mm)evoked [H-3]-D-aspartate overflow (20.4+/-3.5%), which was blocked by A(2A) blocker SCH58261 (0.1 muM). At higher concentrations (10-1000 muM) adenosine inhibited in a DPCPX-sensitive manner the Ca2+-dependent K+-evoked [H-3]-D-aspartate overflow. The inhibitory effect of adenosine at 1000 muM was significantly increased by SCH58261. This inhibition was antagonized by 1 muM DPCPX. Adenosine did not produce any effect on basal release. 3 The A(2A) receptor agonist CGS 21680 was ineffective on basal release, but stimulated the Ca2+-dependent K+-evoked overflow of [H-3]-D-aspartate (EC50 similar or equal to 1 pM). The effect of 0.01 nM CGS 21680 was totally sensitive to the A(2A) receptor antagonist SCH58261 (IC50 similar or equal to 5 nM). 4 The A(1) receptor agonist CCPA inhibited the Ca2+-dependent K+-evoked [H-3]-D-aspartate overflow (EC50 similar or equal to 20 nM). The effect of 100 nM CCPA was abolished by 100 nM of the A(1) receptor antagonist DPCPX. 5 The K+(15 mM)-evoked overflow of endogenous glutamate was enhanced by CGS 21680 (0.01 nM) and inhibited by CCPA (0.1 muM). The effect of CGS 21680 was abolished by SCH58261 (0.1 muM) and that of CCPA by DPCPX (0.1 muM). 6 It is concluded that adenosine and adenosine receptor agonists modulate glutamate release by activating inhibitory A(1) and excitatory A(2A) receptors present on glutamatergic terminals of the rat cerebral cortex.