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

作者：Capannolo Marta; Ciccarelli Carmela; Molteni Raffaella; Fumagalli Fabio; Rocchi Cristina; Romeo Stefania; Fasciani Irene; Aloisi Gabriella; Zani Bianca M; Riva Marco A; Maggio Roberto^*

来源：Epilepsy Research, 2014, 108(1): 11-19.

DOI：10.1016/j.eplepsyres.2013.10.011

• Seizure
• Muscarinic receptor
• Nitric oxide
• Phosphoinositide hydrolysis
• Pilocarpine
• Kainic acid

We investigated how nitric oxide (NO) synthase inhibitor modulates muscarinic receptor expression in epileptic rats. We found that subchronic treatment (4 days) with N-omega-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 N-omega-nitro-L-arginine reduces the down-regulating effect of pilocarpine on carbachol-induced phosphoinositol hydrolysis. Finally, N-omega-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.

• 出版日期2014-1