Seizures selectively impair agonist-stimulated phosphoinositide hydrolysis without affecting protein kinase C activity in rat brain.
The influence of seizures on phosphoinositide hydrolysis and protein kinase C activity was measured in rat hippocampus and cerebral cortex, primarily using a model in which generalized convulsive status epilepticus was induced by administration of LiCl (3 mmole/kg) 20 hr prior to pilocarpine (30 mg/kg). A short (5 min) period of seizures reduced phosphoinositide hydrolysis in hippocampal slices stimulated by norepinephrine or ibotenate, but did not alter the responses to carbachol, 50 mM K+, or NaF. Induction of seizures with diisopropylfluorophosphate caused a similar reduction in the response to norepinephrine without altering carbachol-stimulated phosphoinositide hydrolysis. The inhibition of norepinephrine-stimulated phosphoinositide hydrolysis after seizures generated by lithium plus pilocarpine administration was apparently not due to inhibitory influences of quisqualate or activation of protein kinase C since both of these treatments caused similar inhibitions in slices from control and treated rats. Seizures induced by lithium plus pilocarpine or by kainate did not alter the activity of protein kinase C or the distribution of protein kinase C between membrane and cytosolic fractions. Thus, seizures cause a neurotransmitter-selective impairment of phosphoinositide hydrolysis, and this response may play a role in the severity or duration of seizure activity.
Jope
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RS
Department of Psychiatry and Behavioral Neurobiology, University of Alabama, Birmingham 35294.
Kolasa
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Song
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Ormandy
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D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects; D006868:Hydrolysis; D066298:In Vitro Techniques; D008094:Lithium; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*; D010862:Pilocarpine; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism*
D010716:Phosphatidylinositols; D010862:Pilocarpine; D015240:Phorbol 12,13-Dibutyrate; D008094:Lithium; D011493:Protein Kinase C; D009638:Norepinephrine