Interaction of leptin and nitric oxide pathway on penicillin-induced epileptiform activity in rats.
The aim of the present study was to investigate the role of NO as a mediator of leptin action at the penicillin-induced epileptiform activity in rat. Thirty minutes after penicillin injection, leptin, at a dose of 1 microg, significantly increased the mean frequency of epileptiform activity without changing the amplitude. The effects of systemic administration of nitric oxide synthase (NOS) inhibitors, non-selective NG-nitro-L-arginine methyl ester (L-NAME), selective neuronal NOS inhibitor, 7-nitroindazole (7-NI) and NO precursor, L-arginine on the effects of leptin were investigated. The occurrence of anticonvulsant activity of 7-NI (40 mg/kg, i.p.) was significantly delayed in the presence of leptin (1 microg). The administration of L-NAME (60 mg/kg, i.p.), 30 min before leptin (1 microg) application, did not influence proconvulsant activity of leptin. The administration of L-arginine (1000 mg/kg, i.p.) 30 min before the effective dose of leptin (1 microg, i.c.v.) reversed the proconvulsant effects of leptin whereas the same dose of its inactive enantiomer, D-arginine (1000 mg/kg, i.p.) failed to influence the proconvulsant effect of leptin. The electrophysiological evidence of the present study suggests that neuronal NOS/NO pathway is involved in mediating leptin effects on penicillin-induced epileptiform activity.
Aslan
Ali
A
Department of Physiology, Faculty of Medicine, University of Ondokuz Mayis, Samsun, Turkey.
Yildirim
Mehmet
M
Ayyildiz
Mustafa
M
Güven
Ayla
A
Agar
Erdal
E
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001120:Arginine / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003292:Convulsants / Q000633:toxicity; D004569:Electroencephalography / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007191:Indazoles / Q000494:pharmacology; D020738:Leptin / Q000378:metabolism*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010406:Penicillins / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D000927:Anticonvulsants; D003292:Convulsants; D004791:Enzyme Inhibitors; D007191:Indazoles; D020738:Leptin; D010406:Penicillins; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester