ADENOSINE RECEPTORS MODULATE [CA2+](I) IN HIPPOCAMPAL ASTROCYTES IN-SITU

Cultured astroglia express both adenosine and AIP purinergic receptors that are coupled to increases in intracellular calcium concentration ([Ca2+]i). Currently, there is little evidence that such purinergic receptors exist on astrocytes in vivo. To address this issue, calcium-sensitive fluorescent dyes were used in conjunction with cenfocal microscopy and immunocytochemistry to examine the responsiveness of astrocytes in acutely isolated hippocampal slices to purinergic neuroligands. Both ATP and adenosine induced dynamic increases in astrocytic [Ca2+]i that were blocked by the adenosine receptor antagonist 8-(p-sulfophenyl)theophylline. The responses to adenosine were not blocked by tetrodotoxin, 8-cyclopentyltheophylline, 8-(3-chlorostyryl)caffeine, dipyridamole, or removal of extracellular calcium, The P-2y-selective agonist 2-methylthioadenosine triphosphate was unable to induce increases in astrocytic [Ca2+]i, whereas the P-2 agonist adenosine 5'-O-(2-thiodiphosphate) induced astrocytic responses in a low percentage of astrocytes. These results indicate that the majority of hippocampal astrocytes in situ contain P-1 purinergic receptors coupled to increases in [Ca2+]i, whereas a small minority appear to contain P-2 purinergic receptors. Furthermore, individual hippocampal astrocytes responded to adenosine, glutamate, and depolarization with increases in [Ca2+]i. The existence of both purinergic and glutamatergic receptors on individual astrocytes in situ suggests that astrocytes in vivo are able to integrate information derived from glutamate and adenosine receptor stimulation.