p2x7like receptor activation in astrocytes increases chemokine monocyte chemoattractant protein1 expression via mitogenactivated protein kinase leukocyte infiltration in the cns after trauma or inflammation is triggered in part by upregulation of the chemokine monocyte chemoattractant protein1 mcp1 in astrocytes however the signals that induce the upregulation of mcp1 in astrocytes are unknown we have investigated the roles for atp p2x7 receptor activation because atp is an intercellular signaling transmitter that is released in both trauma and inflammation and p2x7 receptors are involved in immune system signaling astrocytes in primary cell culture and acutely isolated from the hippocampus were immunopositive for p2x7 receptors in astrocyte cultures application of the selective p2x7 agonist benzoylbenzoyl atp bzatp activated map kinases extracellular signal receptoractivated kinase 1 erk1 erk2 and p38 purinergic antagonists depressed this activation with a profile suggesting p2x7 receptors bzatp also increased mcp1 expression in cultured astrocytes and again p2x7 antagonists prevented this increase blocking either the erk1erk2 or the p38 pathway with pd98059 or sb203580 respectively significantly inhibited bzatpinduced mcp1 expression coapplication of both antagonists caused a greater depression we also tested the roles for atp receptor activation in inducing mcp1 upregulation in corticectomy an in vivo model of trauma this model of cortical trauma was previously shown to increase mcp1 expression in vivo principally in astrocytes suramin a widespectrum purinergic receptor antagonist significantly depressed the rapid 3 hr traumainduced increase in mcp1 mrna these data indicate that purinergic transmitter receptors in astrocytes are important in regulating chemokine synthesis the regulation of mcp1 in astrocytes by atp may be important in mediating communication with hematopoietic inflammatory cells