SIGNALING BY ATP RECEPTORS IN ASTROCYTES

TREATMENT of primary cultures of rat cerebral cortical astrocytes with extracellular ATP caused a 3- to 4-fold stimulation of mitogen-activa ted protein (MAP) kinase activity. Studies with agonists and antagonis ts of P-1 and P-2 purinergic receptors indicated that this activation is mediated by ATP/P-2 purinergic receptors rather than adenosine/P-1 purinergic receptors. Increased cAMP levels did not significantly inhi bit the activation of MAP kinase by ATP but did inhibit the stimulatio n of MAP kinase by basic fibroblast growth factor, a polypeptide growt h factor that activates the Ras/Raf kinase signaling pathway. These da ta indicate that ATP/P-2 purinergic receptors are coupled to MAP kinas e by a signal transduction pathway that is independent of the Raf kina se pathway.