Nitric oxide synthase inhibition reverts muscarinic receptor down-regulation induced by pilocarpine- and kainic acid-evoked seizures in rat fronto-parietal cortex.
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.
Biotechnological and Applied Clinical Sciences Department, University of L'Aquila, Via Vetoio - Coppito 2, 67100 L'Aquila, Italy.
Marta
M
Capannolo
Biotechnological and Applied Clinical Sciences Department, University of L'Aquila, Via Vetoio - Coppito 2, 67100 L'Aquila, Italy.
Carmela
C
Ciccarelli
Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti 9, 20133 Milan, Italy.
Raffaella
R
Molteni
Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti 9, 20133 Milan, Italy.
Fabio
F
Fumagalli
Biotechnological and Applied Clinical Sciences Department, University of L'Aquila, Via Vetoio - Coppito 2, 67100 L'Aquila, Italy.
Cristina
C
Rocchi
Biotechnological and Applied Clinical Sciences Department, University of L'Aquila, Via Vetoio - Coppito 2, 67100 L'Aquila, Italy.
Stefania
S
Romeo
Biotechnological and Applied Clinical Sciences Department, University of L'Aquila, Via Vetoio - Coppito 2, 67100 L'Aquila, Italy.
Irene
I
Fasciani
Biotechnological and Applied Clinical Sciences Department, University of L'Aquila, Via Vetoio - Coppito 2, 67100 L'Aquila, Italy.
Gabriella
G
Aloisi
Biotechnological and Applied Clinical Sciences Department, University of L'Aquila, Via Vetoio - Coppito 2, 67100 L'Aquila, Italy.
Bianca M
BM
Zani
Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti 9, 20133 Milan, Italy.
Marco A
MA
Riva
Biotechnological and Applied Clinical Sciences Department, University of L'Aquila, Via Vetoio - Coppito 2, 67100 L'Aquila, Italy. Electronic address: roberto.maggio@univaq.it.
Roberto
R
Maggio
D000818:Animals; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005625:Frontal Lobe / Q000187:drug effects / Q000201:enzymology; D007608:Kainic Acid / Q000037:antagonists & inhibitors / Q000633:toxicity*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009924:Organ Culture Techniques; D010296:Parietal Lobe / Q000187:drug effects / Q000201:enzymology; D010862:Pilocarpine / Q000037:antagonists & inhibitors / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000378:metabolism*; D012640:Seizures / Q000139:chemically induced / Q000201:enzymology*
D004791:Enzyme Inhibitors; D011976:Receptors, Muscarinic; D010862:Pilocarpine; D019001:Nitric Oxide Synthase; D007608:Kainic Acid; D019331:NG-Nitroarginine Methyl Ester
Kainic acid; Muscarinic receptor; Nitric oxide; Phosphoinositide hydrolysis; Pilocarpine; Seizure