1993 Fiscal Year Final Research Report Summary
Study on brain functional mechanism of Ca antagonists with consideration of neuron-glia interaction.
| Project/Area Number |
04671419
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | Tokyo Medical College |
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Principal Investigator |
WATANABE Yasuo Tokyo Medical College, School of Medicine, Associate Professor, 医学部, 助教授 (70183720)
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| Project Period (FY) |
1992 – 1993
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| Keywords | cytosolic Ca^<2+> / Ca antagonists / central acting drugs / glia cells / glutamate / neuron-glia interaction / neuronal damage / cultured cerebellar granule cells |
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| Research Abstract |
In order to search the significane of neuron-glia interaction on going to discuss about the central effects of Ca antagonists, the inhibitory effects of Ca antagonists on glutamate(Glu) induced-cytosolic Ca^<2+> increase and -neuronal damage were measured using by either glia-poor or glia-rich cultured cerebellar granule cells. Dosages between 0.5 and 10muM of flunarizine, nicardipine, SM6586 and SM12565 reduced the rise in [Ca^<2+>]i induced by 50mM KC1 in a dose-dependent manner, although diltiazem, verapamil and nifedipine showed less effects on such [Ca^<2+>]i increases. SM6586 and SM12565 and flunarizine at dosages below 10muM each reduced the magnitude of the [Ca^<2+>]i increase induced by 25muM Glu, but other examined Ca antagonists were less effective.
In the neuronal damage induced by Glu, the pretreatment of SM6586, SM12565 and flunarizine significantly protected. And these protections were much influenced by the co-existence of glia cells. These results suggest that the neuronal protective action of Ca antagonists have to be examined with consideration of neuron-glia interaction.
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