| Project/Area Number |
03670094
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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 |
General pharmacology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
IINO Masamitsu Univ. Tokyo, Fac. Med, Dept. Pharmacol, Lecturer, 医学部(医), 講師 (50133939)
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| Project Period (FY) |
1991 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1992: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1991: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | Calcium / Inositol trisphosphate / smooth muscle / caged compounds / planar bilayer / カルシウムイオン / イノシト-ルミリン酸 / カルシウムストア / 人工膜 |
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| Research Abstract |
Inositol 1,4,5-trisphosphate (IP_3)-induced Ca^<2+> release is an important mechanism that controls the cytoplasmic concentration of Ca^<2+> in the smooth muscle cells. Our previous study on the mechanism of IP_3-induced Ca^<2+> release showed that the Ca^<2+> release channels are regulated by Ca^<2+> and adenine nucleotides. This study was conducted to look into the molecular mechanism of the modulation of IP_3-induced Ca^<2+> release by Ca^<2+> itself. The original intention was to study the single channel activities of the IP_3 channels incorporated into planar lipid bilayers. Although we were successful in obtaining Ca^<2+>-induced Ca^<2+> release channel activities derived from both skeletal muscle and cerebellar microsomal fractions, we found it difficult to obtain aimed results on IP_3 channels within the period of the current study. We, thus, took an alternative course and used caged compounds to study the immediate effects of Ca^<2+> on the IP_3 channels in skinned smooth muscle fibers. It was shown that Ca^<2+> has the immediate potentiating and inhibitory effects on the IP_3-induced Ca^<2+> release, suggesting that Ca^<2+> directly regulates the gating of the IP_3 channels. It was also found that there is a weak cooperativity (Hill coefficient of -2) in the IP_3 dependence of the channel activity. These results are important in the understanding of the physiological regulation of the IP_3-induced Ca^<2+> release in vivo.
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