It has been recently demonstrated that glial cells are active participants of synaptic transmission and brain circuitry. In particular, astrocytes are active players of rapid chemical communication in the brain, but their signalling modes remain largely undefined. Here we show that stimulation of two different receptors for neurotransmitters (mGluR5 for glutamate and B2 for bradykinin) in cultured astrocytes, activates a Ca²⁺-dependent glutamate release which in all cases is sensitive to inhibitors of exocytosis such as tetanus neurotoxin and bafilomycin A1 (-85 % with either agent) suggesting that they share a common mechanism of action which may occur via a mechanism resembling neuronal vesicular release. A surprising feature of this releasing cascade is the inhibition of the glutamate released in the presence of cyclo-oxygenase (COX) blockers such as aspirin and indomethacin (-70/80 % with either agent). The role of the prostaglandins (PGs) in this mechanism is not fully understood, but we have found with Ca²⁺ imaging studies at the single-cell level that receptor-stimulated [Ca²⁺]_i elevations in astrocytes are dramatically reduced (on average, -60/70 % of the AUC) in about 75 % of cells and completely abolished in the others, in the presence of COX inhibitors. Moreover, receptor stimulation is accompanied by PGE₂ formation and its release in extracellular medium, suggesting that PGs are implicated in the amplification of the Ca²⁺ signalling and cell-to-cell communication in the astrocytic network. Finally, administration of exogenous PGE₂ produced per se rapid, store-dependent, Ca²⁺ responses. All these data indicate that : (a) COX-dependent [Ca²⁺]_i elevations are necessary for glutamate release; (b) COX products are responsible for a major component of astrocyte [Ca²⁺]_i elevations in response to glutamate or bradykinin; (c) a large part (albeit not all) of such a component is sustained by the autocrine/paracrine action of PGE₂.

All procedures accord with current National guidelines.