Functional significance of stimulatory GTP-binding protein in hippocampus is associated with kindling-elicited epileptogenesis.
In order to evaluate the involvement of the stimulatory G-protein (Gs)-related transduction system in the basic mechanisms of epilepsy, we examine the expression levels of Gsalpha 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 Gsalpha mRNA expression level in the bilateral hippocampus at 24h after the last generalized seizure. The [3H]-GTP-binding assay with isoproterenol (IPN), a beta-receptor agonist, revealed a remarkable increase of Bmax values in the sham-operated control and partially kindled groups. However, the IPN-induced increase of Bmax 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 Gs function and beta-adrenergic receptor-Gs 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 Gs-related transduction system might have a lesser impact on the acquisition process of epileptogenesis.
Iwasa
H
H
Department of Neuropsychiatry, School of Medicine, Chiba University, Japan. iwasa@med.m.chiba-u.ac.jp
Kikuchi
S
S
Mine
S
S
Sugita
K
K
Miyagishima
H
H
Hasegawa
S
S
D000818:Animals; D004829:Epilepsy, Generalized / Q000503:physiopathology*; D019204:GTP-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D006624:Hippocampus / Q000503:physiopathology*; D007696:Kindling, Neurologic / Q000502:physiology*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*
D012333:RNA, Messenger; D019204:GTP-Binding Proteins