Biotechnological and Applied Clinical Sciences Department, University of L'Aquila, Via Vetoio - Coppito 2, 67100 L'Aquila, Italy.
Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti 9, 20133 Milan, Italy.
Epilepsy Res. 2014 Jan;108(1):11-9. doi: 10.1016/j.eplepsyres.2013.10.011. Epub 2013 Oct 28.
We 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.
我们研究了一氧化氮 (NO) 合酶抑制剂如何调节癫痫大鼠中的毒蕈碱受体表达。我们发现，亚慢性治疗（4 天）用 Nω-硝基-L-精氨酸减少了 pilocarpine 和 kainic 酸诱导的大鼠额顶叶皮质中毒蕈碱受体的下调，尽管这两种致惊厥剂引起的癫痫发作明显增强。此外，额顶叶皮质切片的功能实验表明，Nω-硝基-L-精氨酸可降低 pilocarpine 对 carbachol 诱导的磷酸肌醇水解的下调作用。最后，Nω-硝基-L-精氨酸大大增强了 pilocarpine 诱导的碱性成纤维细胞生长因子 (FGF2) 的诱导。这些数据表明，NO 在调节癫痫发作期间毒蕈碱受体信号的反馈环中可能发挥作用。NO 合酶抑制剂在一些癫痫动物模型中对癫痫发作的强烈增强可能源于阻止这种反馈环。
