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

• Nω-nitro-l-arginine potentiates the convulsant effect of pilocarpine and kainic acid.
• Pilocarpine and kainic acid induce the down-regulation of muscarinic receptors.
• Pre-treatment with Nω-nitro-l-arginine prevents the reduction of muscarinic receptors induced by pilocarpine.
• Pre-treatment with Nω-nitro-l-arginine greatly increase the induction of FGF2 mRNA expression by pilocarpine.

SummaryWe investigated how nitric oxide (NO) synthase inhibitor modulates muscarinic receptor expression in epileptic rats. We found that subchronic treatment (4 days) with Nω-nitro-l-arginine reduced the down-regulation of muscarinic receptors induced by pilocarpine and kainic acid in rat fronto-parietal cortex, notwithstanding the dramatic potentiation of seizures induced by both convulsants. Furthermore, functional experiments in fronto-parietal cortex slices, showed that Nω-nitro-l-arginine reduces the down-regulating effect of pilocarpine on carbachol-induced phosphoinositol hydrolysis. Finally, Nω-nitro-l-arginine greatly 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 muscarinic receptor signal during seizures. The dramatic potentiation of convulsions by NO synthase inhibitors in some animal models of seizures could derive from preventing this feedback loop.