Cyclooxygenase-2/PGE2 pathway facilitates pentylenetetrazol-induced seizures.

Abstract

Cyclooxygenases (COXs) are rate-limiting enzymes in the metabolic pathways in which arachidonic acid is converted to prostaglandins. COX-2 is the isoform induced at injury/inflammation sites and expressed constitutively in a few tissues, such as the central nervous system, and plays a role in neurodegenerative diseases associated with increased excitatory activity. However, the role of COX-2 and its main product, prostaglandin E(2) (PGE(2)), in the convulsive states is not fully established. In this study we showed that the selective COX-2 inhibitor, celecoxib (at the dose of 2mg/kg, but not at the doses of 0.2 or 20mg/kg, p.o.), protects against the seizures induced by pentylenetetrazol (PTZ, 60 mg/kg, i.p.). The role of PGE(2) in the convulsions induced by PTZ was further investigated by administering anti-PGE(2) antibodies (4 microg/2 microl, i.c.v.), and assessing electroencephalographic changes induced by PTZ (PTZ, 60 mg/kg, i.p.). Anti-PGE(2) antibodies attenuated PTZ-induced seizures in rats. In addition, combining PGE(2) (100 ng/2 microl, i.c.v.) with a subconvulsant dose of PTZ (20mg/kg, i.p.) caused seizures, further supporting a role for this prostaglandin in the convulsions induced by PTZ. Finally, we showed that the anticonvulsant action of celecoxib (2mg/kg, p.o.) was reversed by the intracerebroventricular administration of PGE(2) (10 ng/2 microl, i.c.v.). These data constitute strong converging pharmacological evidence supporting a facilitatory role for the COX-2/PGE(2) pathway in the seizures induced by PTZ. However, whether selective COX-2 inhibitors are safer anti-inflammatory drugs for epileptic patients than nonspecific inhibitors remains to be determined.

DOI: 10.1016/j.eplepsyres.2007.12.008

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@article{Oliveira2008Cyclooxygenase2PGE2PF, title={Cyclooxygenase-2/PGE2 pathway facilitates pentylenetetrazol-induced seizures.}, author={Mauro Schneider Oliveira and Ana Fl{\'a}via Furian and Luiz Fernando Freire Royes and Michele Rechia Fighera and Nat{\'a}lia Gindri Fiorenza and Marcelo Castelli and Pablo Machado and Denise Bohrer and Marlei Veiga and Juliano Lino Ferreira and Esper Abra{\~a}o Cavalheiro and Carlos Fernando Mello}, journal={Epilepsy research}, year={2008}, volume={79 1}, pages={14-21} }