Neuroprotective effect of protein kinase C inhibitors on oxygen/glucose free-induced decreases in 2-deoxyglucose uptake and CA1 field potentials in rat hippocampal slices.
Staurosporine, a protein kinase C inhibitor, was found to produce a neuroprotective effect against an ischemic insult in both gerbils and rats in vivo. We have demonstrated that rat hippocampal slices exposed to oxygen/glucose-free medium showed decreases in 2-deoxyglucose (2-DG) uptake and CA1 field potentials elicited by the stimulation of Schaffer collaterals. Therefore we examined the effect of protein kinase C inhibitors on oxygen/glucose free-induced impairments of 2-DG uptake and CA1 field potentials. Pretreatment with staurosporine, K252a and H-7 attenuated decreases in 2-DG uptake and CA1 field potentials. Treatment with phorbol ester, a protein kinase C activator, for a long period (90 min) was found to induce a down-regulation of protein kinase C activity. Therefore we examined the effect of pretreatment with phorbol ester for 90 min on oxygen/glucose free-induced decreases in 2-DG uptake and CA1 field potentials. These decrements were not attenuated by 5-min treatment with phorbol ester but were attenuated by 90-min treatment. The present results suggest that the treatment which decreases protein kinase C activity shows a neuroprotective action against oxygen/glucose free-induced deficits of metabolic and synaptic activity in hippocampal slices.
Shibata
S
S
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Tominaga
K
K
Kagami-ishi
Y
Y
Watanabe
S
S
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D003470:Culture Media; D003847:Deoxyglucose / Q000378:metabolism*; D004734:Energy Metabolism / Q000502:physiology; D005947:Glucose / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D010100:Oxygen / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D019311:Staurosporine
D000470:Alkaloids; D003470:Culture Media; D010703:Phorbol Esters; D003847:Deoxyglucose; D011493:Protein Kinase C; D019311:Staurosporine; D005947:Glucose; D010100:Oxygen