Nitric oxide interacts with oxygen free radicals to evoke the release of adenosine and adenine nucleotides from rat hippocampal slices

The present study examined some possible mechanisms underlying the previous ly demonstrated release of adenosine by nitric oxide (NO) donors. Perfusion with the NO-donor S-nitroso-N-acetyl penicillamine (SNAP; 300 mu M) led to a significant increase in the release of [H-3]purines from both unstimulat ed and electrically stimulated hippocampal slices prelabeled with [H-3]aden ine. The NO-donor also evoked the release of endogenous ATP and ADP from un stimulated slices and, when combined with electrical stimulation the releas e of ATP, AMP and adenosine. The SNAP-induced [H-3]purine release was calci um-dependent, but not affected by the glutamate receptor antagonists MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo[a, d]-cyclohepten-5-10-imine: 100 n M) and CNQX (6-cyano-7-nitroquinoxaline-2,3-dione: 10 mu M). Zaprinast (5 m u M), an inhibitor of the cyclic GMP-dependent phosphodiesterase and 8-Br-c yclic GIMP (0.01-1 mM) failed to evoke the release of purines, whereas gene ration of oxygen free radicals by xanthine plus xanthine oxidase did evoke purine release. Coperfusion of SNAP with the free radical scavengers supero xide dismutase (SOD: 60 mu g/ml) and catalase (50 mu g/ml) reduced or elimi nated the ability of the NO-donor to enhance [H-3]purine release, but the p oly (ADP-ribusyl) synthetase (PARS) inhibitor benzamide (500 mu M) did not affect it. These data indicate that NO interacts with superoxide, likely fo rming peroxynitrite, which subsequently acts to release adenosine and adeni ne nucleotides from hippocampal tissue. (C) 2000 Elsevier Science B.V. All rights reserved.