Rat astroglial P2Z (P2X7) receptors regulate intracellular calcium and purine release

Treatment of rat astrocyte cultures with 2'- and 3'-O-(4-benzoylbenzoyl)-adenosine 5'-triphosphate (BzATP), a P2X7 agonist, but not with adenosine 5-[alpha, beta methylene] triphosphate (alpha, beta meATP), a P2X agonist, increased influx of extracellular Ca2+ and [Ca2+]i. Lucifer yellow, a small molecule which permeates P2X7 receptor-induced pores, entered BzATP-treated but not control astrocytes. BzATP also stimulated efflux of [3H]purine from cultured astrocytes. The P2X7 receptor antagonist oxidized ATP abolished the effects of BzATP on [Ca2+]i, lucifer yellow permeation and [3H]purine release, indicating that these effects were due to P2X7 receptor activation. In neurological diseases or injuries extracellular ATP may activate P2X7 receptors further enhancing [3H]purine release, with important pathophysiological consequences.