ADENOSINE ENHANCES INTRACELLULAR CA2+ MOBILIZATION IN CONJUNCTION WITH METABOTROPIC GLUTAMATE-RECEPTOR ACTIVATION BY T-ACPD IN CULTURED HIPPOCAMPAL ASTROCYTES

2Cl-Adenosine, a non-metabolized adenosine agonist, enhanced the increase in intracellular Ca2+ concentration ([Ca2+](i)) in cultured hippocampal astrocytes induced by (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (t-ACPD), a metabotropic glutamate agonist. In the absence of 2Cl-adenosine, the half effective concentration (EC(50)) of t-ACPD was about 80 mu M. On the other hand, in the presence of 1 mu M 2Cl-adenosine, the EC(50) of t-ACPD shifted to about 5 mu M, although the maximum [Ca2+](i) did not change. The synergistic effect of 2Cl-adenosine with t-ACPD on [Ca2+](i) elevation was not inhibited by the elimination of extracellular Ca2+, but was inhibited by A(1)-specific adenosine antagonists. These results indicate that adenosine can act via the A(1) receptor as an endogenous co-activator of the metabolic processes induced by metabotropic glutamate receptor activation.