EFFECTS OF CIGARETTE-SMOKE ON NITRIC OXIDE-INDUCED INCREASE IN CYCLIC-GMP IN NERVE-TERMINALS OF RAT CEREBRAL-CORTEX

Since nitric oxide (NO) has been widely accepted as a novel neuromodul ator, which activates soluble forms of guanylate cyclase to increase i n guanosine 3':5'-cyclic monophosphate (cyclic GMP) levels, the effect of water-soluble substance in cigarette smoke on cyclic GMP levels we re investigated using nerve terminals prepared from rat cerebral corte x. Although the smoke-substance itself failed to affect cyclic GMP lev els in the synaptosomes, the smoke-substance significantly inhibited t he increases in cyclic GMP levels induced by NO donors. The blocking e ffect of the smoke-substance was inhibited by concomitant incubation w ith superoxide dismutase, but not with mannitol. In addition, the effe ct of smoke-substance was mimicked by products of the xanthine/xanthin e oxidase system, but not by nicotine. The effect of smoke-substance w as preserved at least 7 days after they were stored at room temperatur e. Therefore, these results suggest that the smoke-substance may posse ss long half-lives to produce the radicals which inactivate NO, and to inhibit the increase in cyclic GMP levels in nerve terminals. The int erference with NO may explain the part of mechanism in effects of ciga rette smoke on neuronal functions.