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 (EC50) of t-ACPD was about 80 microM. On the other hand, in the presence of 1 microM 2Cl-adenosine, the EC50 of t-ACPD shifted to about 5 microM, 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 A1-specific adenosine antagonists. These results indicate that adenosine can act via the A1 receptor as an endogenous co-activator of the metabolic processes induced by metabotropic glutamate receptor activation.