P. Schubert et al., MODULATION OF NERVE AND GLIAL FUNCTION BY ADENOSINE - ROLE IN THE DEVELOPMENT OF ISCHEMIC DAMAGE, International Journal of Biochemistry, 26(10-11), 1994, pp. 1227-1236
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.