Nitric oxide synthase inhibition reverts muscarinic receptor down-regulation induced by pilocarpine- and kainic acid-evoked seizures in rat fronto-parietal cortex.

Summary We investigated how nitric oxide (NO) synthase inhibitor modulates muscarinicreceptor expression in epileptic rats. We found that subchronic treatment (4 days) with N ω - nitro-l- argininereduced the down-regulation of muscarinicreceptors induced by pilocarpineand kainic acidin rat fronto-parietal cortex, notwithstanding the dramatic potentiation of seizures induced by both convulsants. Furthermore, functional experiments in fronto-parietal cortex slices, showed that N ω - nitro-l- argininereduces the down-regulating effect of pilocarpineon carbachol-induced phosphoinositol hydrolysis. Finally, N ω - nitro-l- argininegreatly potentiated the induction of basic fibroblast growth factor(FGF2) by pilocarpine. These data suggest a potential role of NO in a regulatory feedback loop to control muscarinicreceptor signal during seizures. The dramatic potentiation of convulsionsby NO synthase inhibitors in some animal models of seizures could derive from preventing this feedback loop.