Adenosine enhanced intracellular Ca²⁺ concentrations in astrocytes via A_2a adenosine receptors involving protein kinase A (PKA) activation. The Ca²⁺ rise is inhibited by brefeldin A, an inhibitor of vesicular transport; but not by neomycin and U73122, phospholipase C inhibitors; xestospongin, an IP₃-receptor inhibitor; ryanodine, a ryanodine-receptor inhibitor; TMB-8, an endoplasmic reticulum calcium-release blocker; octanol, a gap-junction inhibitor; or cadmium, a non-selective, calcium-channel blocker. Adenosine stimulates astrocytic glutamate release via an A_2a adenosine receptors/PKA pathway, and the release is inhibited by the vesicular transport inhibitors brefeldin A and bafilomycin A1. A_2a adenosine receptors and the ensuing PKA events, thus, are endowed with vesicular Ca²⁺ release from an unknown intracellular calcium store and vesicular glutamate release from astrocytes.