Functional significance of stimulatory GTP-binding protein in hippocampus is associated with kindling-elicited epileptogenesis

Abstract

In order to evaluate the involvement of the stimulatory G-protein (G(s))-related transduction system in the basic mechanisms of epilepsy, we examine the expression levels of G(sα) mRNA and specific GTP-binding ability in the hippocampus of amygdaloid-kindled rats at various seizure stages. Northern blot analysis showed a significant increase in the G(sα) mRNA expression level in the bilateral hippocampus at 24 h after the last generalized seizure. The [3H]-GTP-binding assay with isoproterenol (IPN), a β-receptor agonist, revealed a remarkable increase of B(max) values in the sham-operated control and partially kindled groups. However, the IPN-induced increase of B(max) values was abolished on both sides of the hippocampus at 24 h after and at 4 weeks after the last generalized seizure in fully kindled rats. These data suggest that alteration in the G function and β-adrenergic receptor-G(s) coupling might be implicated in the neurobiological basis of the induction mechanisms of the generalization of seizures and the mechanisms of the maintenance of enduring epileptogenesis. Conversely, the G(s)-related transduction system might have a lesser impact on the acquisition process of epileptogenesis.