Cognato Giana de Paula, Bruno Alessandra Nejar, da Silva Rosane Souza, Bogo Maurício Reis, Sarkis João José Freitas, Bonan Carla Denise
Laboratório de Enzimologia, Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Neurochem Res. 2007 Jun;32(6):1046-55. doi: 10.1007/s11064-006-9272-y. Epub 2007 Mar 31.
Ecto-nucleotidases, one of the main mechanisms involved in the control of adenosine levels in the synaptic cleft, have shown increased activities after the pilocarpine model of epilepsy. Here we have investigated the effect of the antiepileptic drugs (AEDs) on ecto-nucleotidase activities from hippocampal and cerebral cortical synaptosomes of rats at seven days after the induction of the pilocarpine model. Expression of these enzymes were investigated as well. Our results have demonstrated that phenytoin (50 mg/kg) and carbamazepine (30 mg/kg) were able to prevent the increase in ecto-nucleotidase activities elicited by pilocarpine in brain synaptosomes. However, sodium valproate (at 100 mg/kg) was only able to avoid the increase on ATP and ADP hydrolysis in hippocampal synaptosomes. Increase on ATP hydrolysis in hippocampal synaptosomes was also prevented by sodium valproate at 286 mg/kg, which corresponds to ED50 for pilocarpine model. NTPDase1, NTPDase2, NTPDase3, and ecto-5'-nucleotidase expressions were not affected by pilocarpine in cerebral cortex. However, expressions of NTPDase2, NTPDase3, and ecto-5'-nucleotidase were increased by pilocarpine in hippocampus. Our results have indicated that previous treatment with AEDs was able to prevent the increase in hippocampal ecto-nucleotidases of pilocarpine-treated rats. These findings have shown that anticonvulsant drugs can modulate plastic events related to the increase of nucleotidase expression and activities in pilocarpine-treated rats.
外核苷酸酶是参与控制突触间隙中腺苷水平的主要机制之一，在毛果芸香碱癫痫模型后其活性有所增加。在此，我们研究了抗癫痫药物（AEDs）对毛果芸香碱模型诱导7天后大鼠海马和大脑皮质突触体中外核苷酸酶活性的影响。同时也研究了这些酶的表达情况。我们的结果表明，苯妥英（50mg/kg）和卡马西平（30mg/kg）能够预防毛果芸香碱引起的脑突触体中外核苷酸酶活性的增加。然而，丙戊酸钠（100mg/kg）仅能避免海马突触体中ATP和ADP水解的增加。286mg/kg的丙戊酸钠也能预防海马突触体中ATP水解的增加，这相当于毛果芸香碱模型的半数有效剂量（ED50）。在大脑皮质中，NTPDase1、NTPDase2、NTPDase3和外5'-核苷酸酶的表达不受毛果芸香碱影响。然而，在海马中，毛果芸香碱可使NTPDase2、NTPDase3和外5'-核苷酸酶的表达增加。我们的结果表明，预先使用AEDs能够预防毛果芸香碱处理大鼠海马中外核苷酸酶的增加。这些发现表明，抗惊厥药物可以调节与毛果芸香碱处理大鼠中核苷酸酶表达和活性增加相关的可塑性事件。
