Paul Vanaja, Subramanian E Harihara
Department of Pharmacology and Environmental Toxicology, Dr. A.L.M. Postgraduate Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai 600 113, India.
Pharmacol Biochem Behav. 2002 Jun;72(3):515-9. doi: 10.1016/s0091-3057(02)00713-x.
Five, 30, and 60 min pretreatment of 1000 mg/kg and not 500 mg/kg of L-arginine inhibited convulsions induced by picrotoxin. The concentrations of nitric oxide (NO) and gamma aminobutyric acid (GABA) were increased in the brain 5, 30, and 60 min after administration of 1000 mg/kg and not 500 mg/kg of L-arginine. A much higher dose of L-arginine (2000 mg/kg), 30 min after administration, produced a lesser anticonvulsant and NO and GABA increasing actions as compared to that produced by 1000 mg/kg of L-arginine. The same dose of L-arginine, 60 min after administration, decreased the concentrations of both NO and GABA and increased the convulsion frequency of picrotoxin. An NO decreasing dose of nitric oxide synthase (NOS) inhibitor, N-nitro-L-arginine methyl ester (L-NAME) decreased brain GABA concentration and increased the convulsant action of picrotoxin. Further, L-NAME pretreatment prevented L-arginine (1000 mg/kg) from producing anticonvulsant and NO and GABA increasing effects. An interpretation of these results suggests that NO synthesized from systemically administered L-arginine inhibits convulsions by increasing the concentration of GABA in the brain. However, the effects of L-arginine are reversible, if it is administered at a higher dose (2000 mg/kg) 60 min prior to the test. It is concluded that L-arginine produces anticonvulsant or proconvulsant action depending upon the dose and time of its administration-related changes in the concentrations of NO and GABA in the brain.
1000mg/kg而非500mg/kg的L-精氨酸预处理5、30和60分钟可抑制印防己毒素诱发的惊厥。给予1000mg/kg而非500mg/kg的L-精氨酸后5、30和60分钟，大脑中一氧化氮（NO）和γ-氨基丁酸（GABA）的浓度升高。给药30分钟后，更高剂量的L-精氨酸（2000mg/kg）产生的抗惊厥作用以及使NO和GABA增加的作用比1000mg/kg的L-精氨酸产生的作用要小。给药60分钟后，相同剂量的L-精氨酸降低了NO和GABA的浓度，并增加了印防己毒素的惊厥频率。一氧化氮合酶（NOS）抑制剂N-硝基-L-精氨酸甲酯（L-NAME）的一个降低NO的剂量降低了大脑GABA浓度，并增强了印防己毒素的惊厥作用。此外，L-NAME预处理可阻止L-精氨酸（1000mg/kg）产生抗惊厥作用以及使NO和GABA增加的作用。对这些结果的一种解释表明，全身给药的L-精氨酸合成的NO通过增加大脑中GABA的浓度来抑制惊厥。然而，如果在测试前60分钟给予更高剂量（2000mg/kg）的L-精氨酸，其作用是可逆的。得出的结论是，L-精氨酸产生抗惊厥或促惊厥作用取决于其给药剂量和时间，这与大脑中NO和GABA浓度的相关变化有关。
