The present study investigated the effect of adenosine on glial glutamate e
fflux. Adenosine (from 1 nM to 100 muM) enhanced the release from cultured
rat glial cells in a bell-shaped dose-responsive manner for the hippocampus
and in a dose-dependent manner for the superior colliculus, and a similar
increase was obtained with the A(2a) adenosine receptor agonist, 2-p-(2-car
boxyethyl) phenethylamino-5'-N-ethylcarboxamidoadenosine hydrochloride (CGS
21680), but not with the Al adenosine receptor agonist, N-6-cyclohexyladeno
sine (CHA). Adenosine and CGS21680 also enhanced glutamate efflux from Xeno
pus oocytes injected with the poly (A)(+) mRNAs derived from cultured glial
cells for the hippocampus and the superior colliculus together with and wi
thout the A(2a) adenosine receptor mRNA, but instead such increase was not
found in oocytes expressing A(2a) adenosine receptors alone. The results of
the present study thus suggest that adenosine enhances glutamate efflux fr
om glial cells via A(2a) adenosine receptors, and this may represent a mech
anism underlying the facilitatory action of adenosine on hippocampal and su
perior colliculus neurotransmissions. (C) 2001 Elsevier Science Inc. All ri
ghts reserved.