2001 Fiscal Year Final Research Report Summary
Mechanism of extracellular ATP-induced inhibition of store-operated Ca^<2+> entry
| Project/Area Number |
12670038
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General physiology
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
OMATSU Mariko Shiga University of Medical Science, Physiology, Associate Professor, 医学部, 助教授 (80161397)
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| Project Period (FY) |
2000 – 2001
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| Keywords | ATP / P2 receptor / intracellular Ca^<2+> / store-operated Ca^<2+> entry / G-protein coupled receptor / cytoskeleton / actin / brown adipocyte |
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| Research Abstract |
Agonist-induced activation of phospholipase C/Gq produces IP_3 which opens the Ca^<2+> channels in ER in most of the cells. The emptying or even decrease of Ca^<2+> stores triggers the store-operated Ca^<2+> entry across the plasma membrane, which has been recognized to be the major Ca^<2+> influx in non-electric excitable cells. We have reported that the extracellular ATP completely Inhibits the thapsigargin-induced store-operated Ca^<2+> entry in rat primary cultured brown adipocytes. In this project, we investigated the mechanism of the ATP-induced inhibition of the store-operated Ca^<2+> entry and obtained the following results.
1. Extracellular ATP inhibited the store-operated Ca^<2+> entry in the absence of extracellular Mg^<2+> suggesting that the activation of ect-enzymes does not play a role.
2. P2 receptor antagonists suramin. and PPADS suppressed the thapsigargin-induced Ca^<2+> influx as well as the inhibition of the transient Ca^<2+> elevation.
3. Extracellular ATP stimulated the redistribution of actin filaments in peripheral region of the cell (near the plasma membrane).
4. Extracellular ATP enhanced peripheral polymerization of actin in thapsigargin-pretreated cells5. P2 receptor antagonists inhibited the ATP-lnduced peripheral actin polymerization
6. Actin polymerization inhibitor cytochalasin D blocked the effect of ATP, and furthermore, extracellular ATP did not inhibit store-operated Ca^<2+> entry in cytochalasin D-pretreated cells.
These observations suggest that extracellular ATP stimulates the formation of the cortical actin layer mediated through P2 receptors, resulting in blocking the influx of Ca^<2+> in rat brown adipocytes.
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Research Products
(4 results)
