Department of Physiology, Faculty of Medicine, University of Ondokuz Mayis, Samsun, Turkey.
Brain Res. 2010 Mar 19;1321:117-24. doi: 10.1016/j.brainres.2010.01.054. Epub 2010 Jan 29.
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.
本研究旨在探讨一氧化氮 (NO) 在莱菔硫烷诱导的癫痫样活动中作为瘦素作用的中介的作用。在青霉素注射后 30 分钟，瘦素（1 微克）剂量显著增加癫痫样活动的平均频率，而不改变幅度。研究了全身给予一氧化氮合酶 (NOS) 抑制剂、非选择性 NG-硝基-L-精氨酸甲酯 (L-NAME)、选择性神经元 NOS 抑制剂 7-硝基吲唑 (7-NI) 和 NO 前体 L-精氨酸对瘦素作用的影响。在存在瘦素（1 微克）的情况下，7-NI（40mg/kg，ip）的抗惊厥作用发生明显延迟。在给予 L-NAME（60mg/kg，ip）30 分钟前给予瘦素（1 微克）应用，不会影响瘦素的促惊厥活性。在给予有效剂量的瘦素（1 微克，icv）前 30 分钟给予 L-精氨酸（1000mg/kg，ip），可逆转瘦素的促惊厥作用，而其非活性对映体 D-精氨酸（1000mg/kg，ip）的相同剂量则不能影响瘦素的促惊厥作用。本研究的电生理证据表明，神经元 NOS/NO 途径参与介导瘦素对青霉素诱导的癫痫样活动的作用。
