MODULATION OF ISCHEMIA-EVOKED RELEASE OF EXCITATORY AND INHIBITORY AMINO-ACIDS BY ADENOSINE A(1) RECEPTOR AGONIST

Adenosine has been reported to have beneficial effects against ischemi c brain damage, although the mechanisms are not fully clarified. To ex amine the role of adenosine on the ischemia-evoked release of neurotra nsmitters, we applied a highly selective agonist for adenosine A, rece ptor, 2-chloro-N-6-cyclopentyladenosine (CCPA), into the ischemic brai n using in vivo brain dialysis, which directly delivered the agonist t o the local brain area. Concentrations of extracellular amino acids (g lutamate, aspartate, gamma-aminobutyric acid (GABA) and taurine) and r egional blood flow in the striatum of spontaneously hypertensive rats (SHRs) were monitored during cerebral ischemia elicited by bilateral c arotid artery occlusion for 40 min and recirculation. Striatal blood f low and basal levels of amino acids were not affected by direct perfus ion of CCPA (10 mu M or 100 mu M). During ischemia, concentrations of glutamate, aspartate, GABA and taurine increased up to 37-, 30-, 96- a nd 31-fold, respectively, when vehicle alone was administered. Adminis tration of CCPA did not affect the changes in regional blood flow duri ng ischemia and reperfusion. Perfusion of CCPA (100 mu M), however, si gnificantly attenuated the ischemia-evoked release of aspartate (by 70 %) and glutamate (by 73%). The ischemia-induced increase of GABA tende d to be decreased by CCPA, although it was not statistically significa nt. In contrast, both low and high concentrations of CCPA had little e ffect on the release of taurine during ischemia. These results suggest that stimulation of adenosine A(1) receptors selectively attenuated t he ischemia-evoked release of excitatory amino acids, but not of inhib itory amino acids without affecting blood flow. This modulation of the release of amino acids by adenosine A, receptor agonists may play a p rotective role against ischemic neuronal damage. (C) 1998 Elsevier Sci ence B.V. All rights reserved.