MODULATION OF NERVE AND GLIAL FUNCTION BY ADENOSINE - ROLE IN THE DEVELOPMENT OF ISCHEMIC DAMAGE

Adenosine is released during brain ischemia and provides neuroprotecti on by actions on nerve and glial cells. Activation of the adenosine A( 1) receptor enhances the K+ and Cl- conductance in neurons, leading to membrane hyperpolarization and postsynaptic reduction of neuronal Ca2 + influx through voltage- and NMDA receptor-dependent channels. In add ition adenosine A(1) receptor activation decreases excitatory amino ac id release, possibly via inhibition of N- and P-type Ca2+ channels. Th e A(1) and A(2) receptors, coupled to G(i)/G(o) and G(s) proteins resp ectively, often co-exist and interact with the phospholipase C-depende nt activation of the protein kinase C and the adenylyl cyclase. Activa tion of the A(1) receptor may mimic metabotropic receptor stimulation in activating intracellular Ca2+ mobilization and PKC. A(2) receptor m ediated cAMP formation is depressed by high intracellular Ca2+ but enh anced by PKC activation. By modulating these metabolic signaling event s, adenosine may influence acute cell functions, gene transcription an d sustained changes of nerve and glial cells relevant for the developm ent of ischemic damage. The neuroprotective adenosine effect seems to be amplified by treatment with propentofylline, which enhances adenosi ne release, influences the balance between A(1) and A(2) receptor medi ated actions, depresses the free radical formation in activated microg lia and influences astrocyte reactions.