Involvement of the nitric oxide/cyclic guanylate monophosphate pathway in the pilocarpine-induced seizure model in mice.

Abstract

The present study was designed to investigate the involvement of the nitric oxide (NO)/cyclic guanylate monophosphate pathway in pilocarpine-induced seizures in mice. Male Swiss mice (26-32 g) were used as the in vivo model. The following pharmacological tools were utilized: the non-selective NO synthase (NOS) inhibitor L-NAME (10 mg/kg, i.p.), a preferential inducible NOS (iNOS) inhibitor aminoguanidine (25 mg/kg, i.p.), a highly specific iNOS inhibitor 1400W (2.5 mg/kg, i.p.), the NO donor L-arginine (150 mg/kg, i.p.), and the soluble guanylyl cyclase inhibitor ODQ (10 mg/kg, i.p.). The animals were divided into groups (n = 8) and pretreated for 30 min before receiving pilocarpine (400 mg/kg, i.p.), while the control group received only pilocarpine. They were observed for 60 min to measure initial seizure latency, latency till death, and mortality. An administration of L-NAME or ODQ delayed the onset of initial seizure, increased latency till death, and produced a 25% survival rate. Aminoguanidine increased the initial seizure and latency until death, and administration of 1400W did not have an effect. Incremental increases of NO by L-arginine were capable of decreasing the seizure and death latency. These results support the idea that the constitutive NOS, probably neuronal NOS, followed by soluble guanylyl cyclase activation is involved in the convulsive responses caused by pilocarpine administration.

• Authors: Emiliano Ricardo Vasconcelos Rios, Nayrton Flávio Moura Rocha, Alyne Mara Rodrigues Carvalho, Leonardo Freire Vasconcelos, Marília Leite Dias, Camila Nayane de Carvalho Lima, Kamila Soares Lopes, Francisca Helvira Cavalcante Melo, Marta Maria de França Fonteles
• Journal: Pharmacology (Pharmacology) Vol. 91 Issue 3-4 Pg. 131-4 ( 2013) ISSN: 1423-0313 [Electronic] Switzerland
• PMID: 23364440 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 S. Karger AG, Basel.

Chemical References

• 1H-(1,2,4)oxadiazolo(4,3-a)-quiloxalin-1-one
• Amidines
• Benzylamines
• Enzyme Inhibitors
• Guanidines
• N-(3-(aminomethyl)benzyl)acetamidine
• Oxadiazoles
• Receptors, Cytoplasmic and Nuclear
• Pilocarpine
• Nitric Oxide
• Arginine
• Nitric Oxide Synthase
• Guanylate Cyclase
• Soluble Guanylyl Cyclase
• Cyclic GMP
• pimagedine
• NG-Nitroarginine Methyl Ester

Topics

• Amidines (pharmacology)
• Animals
• Arginine (pharmacology)
• Benzylamines (pharmacology)
• Cyclic GMP (metabolism)
• Disease Models, Animal
• Enzyme Inhibitors (pharmacology)
• Guanidines (pharmacology)
• Guanylate Cyclase (antagonists & inhibitors, metabolism)
• Male
• Mice
• NG-Nitroarginine Methyl Ester (pharmacology)
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase (antagonists & inhibitors)
• Oxadiazoles (pharmacology)
• Pilocarpine
• Receptors, Cytoplasmic and Nuclear (antagonists & inhibitors, metabolism)
• Seizures (chemically induced, metabolism)
• Soluble Guanylyl Cyclase