Tese
Receptores EP1 E EP3 modulam as crises epilépticas induzidas por pentilenotetrazol e ácido caínico em camundongos
Fecha
2013-06-27Registro en:
RESCHKE, Cristina Ruedell. EP1 AND EP3 RECEPTORS MODULATE PENTYLENETETRAZOLAND
KAINIC ACID-INDUCED SEIZURES IN MICE. 2013. 185 f. Tese (Doutorado em Farmácia) - Universidade Federal de Santa Maria, Santa Maria, 2013.
Autor
Reschke, Cristina Ruedell
Institución
Resumen
Epilepsy is one of the most common neurologic disorders. It has been suggested that
seizures may be facilitaded by inflammation. PGE2 is one of the most important inflammatory
mediators, and facilitates pentylenetetrazol (PTZ)-induced seizures by stimulating EP1 and
EP3 receptors. However, up to the present moment, no study has investigated whether EP1
and EP3 receptors blocking attenuate seizures induced by convulsants other than PTZ. It is
also unknown whether Na+,K+-ATPase activity alterations are involved in such an effect.
Therefore, in the current study we investigated whether EP1 and EP3 ligands (agonists and
antagonists) modulate PTZ- and kainic acid (KA)-induced seizures, and whether alterations
in Na+,K+-ATPase activity mediate such a protective effect, in mice. EP1 and EP3
antagonists (ONO-8713 and ONO-AE3-240, respectively, 10 Og/kg, s.c.) attenuated PTZ (60
mg/kg, i.p.)- and KA (20 mg/kg, i.p.)-induced seizures. The respective agonists (ONO-DI-004
and ONO-AE-248, 10 Og/kg, s.c.) facilitated seizures in both acute models, and at noneffective
doses, prevented the protective effects of the antagonists. Animals injected with
PTZ presented decreased Na+,K+-ATPase activity in the cerebral cortex and hippocampus.
On the other hand, animals injected with KA presented increased Na+,K+-ATPase activity in
the same cerebral structures at the end of the experiment. These divergent findings suggest
that alterations in Na+,K+-ATPase activity in both acute models depends on the convulsant
agent used and make difficult to establish a relationship between Na+,K+-ATPase activity and
seizure development. Moreover, EP1 and EP3 antagonists administration abolished Na+,K+-
ATPase activity alterations induced by PTZ and KA, in such a way that these alterations
seem to be related more to the presence of ictal phenomenon itself than to the seizure
induction mechanisms. Notwithstanding, the currrent results clearly show that EP1 and EP3
receptors might constitute novel targets for anticonvulsants development, since EP1 and
EP3 decreased seizures, regardless of the convulsant agent used.