Nitric oxide and convulsions in 4-aminopyridine-treated mice.
We studied whether N(G)-nitro-L-arginine (NNA), an inhibitor of nitric oxide (NO) synthase as well as L-arginine and molsidomine, two agents elevating NO, influenced convulsions caused by 4-aminopyridine, a K+ channel blocker in mice. NNA, in a dose known to decrease level of NO (40 mg x kg(-1)), enhanced the seizure susceptibility to intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) 4-aminopyridine. L-arginine (500 mg x kg(-1)) and molsidomine (20 mg x kg(-1)) alone did not influence 4-aminopyridine-induced seizure activity. Surprisingly, the proconvulsant effect of NNA upon clonic and tonic seizures was potentiated by molsidomine (20 mg x kg(-1)). No influence of L-arginine on the proconvulsant effect of NNA was found. Taking into account the proconvulsant effect of NNA, an involvement of NO-mediated events in the mechanism of convulsive activity of 4-aminopyridine might be postulated. However, the ineffectiveness of L-arginine and molsidomine to suppress the convulsive activity of 4-aminopyridine as well as a paradoxical potentiation of the proconvulsant effect of NNA by molsidomine seem to exclude the impact of NO pathway on 4-aminopyridine-induced convulsions in mice. Our data suggest that the proconvulsant effect of NNA in this seizure model is caused by other, not related to NO, mechanisms.
Tutka
Piotr
P
Department of Pharmacology and Toxicology, Medical University of Lublin, Jaczewskiego 8, PL-20-090, Lublin, Poland. tutkap@itsa.ucsf.edu
Młynarczyk
Małgorzata
M
Zółkowska
Dorota
D
Kleinrok
Zdzisław
Z
Wielosz
Marian
M
Czuczwar
Stanisław J
SJ
D015761:4-Aminopyridine / Q000633:toxicity*; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D012640:Seizures / Q000139:chemically induced* / Q000517:prevention & control
D004791:Enzyme Inhibitors; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D015761:4-Aminopyridine; D019001:Nitric Oxide Synthase