KAINATE-EVOKED RELEASE OF ADENOSINE FROM THE HIPPOCAMPUS OF THE ANESTHETIZED RAT - POSSIBLE INVOLVEMENT OF FREE-RADICALS

Using microdialysis in the hippocampus of anaesthetised rats, the conc entration of extracellular adenosine was estimated to be 0.8 mu M. Kai nic acid (0.1-25 mM) in the perfusate evoked a concentration-dependent release of adenosine with an EC(50) of 940 mu M. Two 5-min pulses of 1 mM kainic acid in the perfusate increased the dialysate levels with an S2/S1 ratio of 0.52 +/- 0.03. Kainate-evoked release of adenosine w as reduced significantly by 10 mu M tetrodotoxin and by a kappa-recept or agonist, U50,488H (100 mu M). The S2/S1 ratio was reduced by 4.5 mu M 6-cuano-7-nitroquinoxaline-2,3-dione, a non-NMDA receptor antagonis t, but not by the NMDA receptor blockers (+)-MK-801 (dizocilpine; 100 mu M) or (+/-)-2-amino-5-phosphonopentanoic acid (1 mM), indicating a non-NMDA receptor-mediated process, The S2/S1 ratio was also reduced s ignificantly by 10 mM ascorbic acid, 10 mM glutathione (a scavenger of hydroperoxides), and 1 mM oxypurinol (a xanthine oxidase inhibitor), indicating the possible involvement of free radicals. Neither the aden osine Al receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine (100 m u M) nor the Al adenosine receptor agonist R(-)-N-6-(2-phenylisopropyl )adenosine (100 mu M) affected release. Adenosine release evoked by ka inic acid is therefore mediated by activation of non-NMDA receptors an d may involve the propagation of action potentials and the production of free radicals.