Adenosine enhances glial glutamate efflux via A2a adenosine receptors

The present study investigated the effect of adenosine on glial glutamate efflux. 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-carboxyethyl) phenethylamino-5'-N-ethylcarboxamidoadenosine hydrochloride (CGS21680), but not with the Al adenosine receptor agonist, N-6-cyclohexyladenosine (CHA). Adenosine and CGS21680 also enhanced glutamate efflux from Xenopus oocytes injected with the poly (A)(+) mRNAs derived from cultured glial cells for the hippocampus and the superior colliculus together with and without 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 from glial cells via A(2a) adenosine receptors, and this may represent a mechanism underlying the facilitatory action of adenosine on hippocampal and superior colliculus neurotransmissions. (C) 2001 Elsevier Science Inc. All rights reserved.