Antiepileptic drugs prevent changes induced by pilocarpine model of epilepsy in brain ecto-nucleotidases.
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.
Cognato
Giana de Paula
Gde P
Laboratório de Enzimologia, Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Bruno
Alessandra Nejar
AN
da Silva
Rosane Souza
RS
Bogo
Maurício Reis
MR
Sarkis
João José Freitas
JJ
Bonan
Carla Denise
CD
D000244:Adenosine Diphosphate / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000096:biosynthesis*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D002220:Carbamazepine / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology; D004827:Epilepsy / Q000139:chemically induced* / Q000201:enzymology*; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology; D008297:Male; D018721:Muscarinic Agonists; D010672:Phenytoin / Q000494:pharmacology; D010862:Pilocarpine; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013574:Synaptosomes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D014635:Valproic Acid / Q000494:pharmacology
D000927:Anticonvulsants; D018721:Muscarinic Agonists; D010862:Pilocarpine; D002220:Carbamazepine; D000249:Adenosine Monophosphate; D014635:Valproic Acid; D010672:Phenytoin; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases; C027201:ectoATPase