Neuroprotective Effect of KR-31378 via K_<ATP> Channel Opening against Ischemic Insult(Miscellaneous)

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The opening of the adenosine triphosphate (ATP)-sensitive potassium (K_<ATP>) channel has been proposed as a therapeutic approach for ischemia. Here we examined the opening effect of KR-31378 on the K_<ATP> channel using patch clamp recording in neuroblastoma 2a (N2a) cells and investigated the neuroprotective effect of KR-31378 in organotypic hippocampal slice cultures exposed to oxygen/glucose deprivation. The treatment with KR-31378 (10 μM) to N2a cells seemed to induce K_<ATP> channel opening in a dose dependent manner. The opening effect of KR-31378 was more significant than that of other known K_<ATP> channel openers. Pretreatment with KR-31378 (1O μM) showed a neuroprotective effect in both CA1 and CA3 regions and its effect was attenuated by glibenclamide in a dose dependent manner in both areas. This remarkable neuroprotective effect of KR-31378 seemed to be mediated by the opening of the K_<ATP> channel. These results suggest that KR-31378 could be a possible neuroprotective agent against cerebral ischemia.
公益社団法人日本薬学会の論文
2004-08-01