| Project/Area Number |
11470392
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Functional basic dentistry
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
DOHI Toshihiro Hiroshima University, Faculty of Dentistry, Professor, 歯学部, 教授 (00034182)
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| Co-Investigator(Kenkyū-buntansha) |
MORITA Katsuya Hiroshima University, Faculty of Dentistry, Assistant Professor, 歯学部, 講師 (10116684)
KITAYAMA Shigeo Hiroshima University, Faculty of Dentistry, Associate Professor, 歯学部, 助教授 (80177873)
今井 康夫 広島大学, 歯学部, 助手 (30271068)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥14,500,000 (Direct Cost: ¥14,500,000)
Fiscal Year 2000: ¥6,600,000 (Direct Cost: ¥6,600,000)
Fiscal Year 1999: ¥7,900,000 (Direct Cost: ¥7,900,000)
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| Keywords | Store-operted Ca^<2+> entry / SOC / ROC / trp / calcium / PACAP / PAF / caffeine / Store-operated Ca^<2+> channel / Ca^<2+> チャンネル |
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| Research Abstract |
The receptor-activated Ca^<2+> channels (ROC) activate Ca^<2+> entry which is activated by the depletion of intracellular Ca^<2+> stores, termed store-operated channels (SOC). However, the structure and function of these channels are still unidentified, and the specific blockers are not developed. The present study was undertaken to elucidate the mechanisms for the activation of and the signal transduction relate to ROC/SOC, and inhibitors for the channels.
1 COS cells were expressed with rat TRP by introducing rtrp3 and rtrp6. These COS cells were treated with thapsigargin in the absence of extracellular Ca^<2+> to acivate SOC.Large Ca^<2+> entry was observed in these cells. PC12 cells expressed dominantly trp1 and trp3. In PC12 cells introduced trp1,3 antisense mRNA, Ca^<2+> entry evoked by the pre-treatment of acetylcholine and thapsigargine was enhanced. These results may suggest that TRPs do not simply compose the Ca^<2+> channel itself but relate somehow with SOC systems.
2 12-hydr
… More
oxyeicosatetraenoic acid (12-HETE), a mediator of inflammation. activates neutrophils through the rise of intracellular free Ca^<2+> concentration ([Ca^<2+>]i). However, the mechanism of Ca^<2+> rise was not evident. 12-HETE-induced [Ca^<2+>]i rise was blocked by platelet-activating factor(PAF) antagonist, PAF synthesis inhibitor and 12-HETE stimulated PAF production in human and rabbit neutophils. These results suggested that 12-HETE-induced [Ca^<2+>]i rise is mediated by PAF.FMLP-but not LTB_4-induced [Ca^<2+>]i rise was partly mediated by PAF.
3 Pituitary adenylate cyclase activating polypeptide (PACAP) induced long-lasting increase in [Ca^<2+>]i and catecholamine release from bovine adrenal chromaffin cells. PACAP-induced ([Ca^<2+>]i rise was not mediated by cyclic AMP, phospholipase C, cyclic ADP-ribose, voltage-dependent Na+ channels, voltage-dependent Ca^<2+> channels. Pre-activation of SOC did not modify PACAP-induced Ca^<2+> entry. GdCl_2 blocked SOC but did not affect PACAP-induced Ca^<2+> entry. These results suggested that PACAP activates ROC which is distinguishable form SOC.
4 Caffeine and theophylline were found to block [Ca^<2+>]i rise and Ca^<2+> entry induced by acetylcholine, thapsigargine and TPEN in bovine adrenal chromaffin cells. Less
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