2006 Fiscal Year Final Research Report Summary
Identification of a specific transporter on extracellular release of ATP
| Project/Area Number |
17590234
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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 pharmacology
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| Research Institution | Fukuoka University |
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Principal Investigator |
KATSURAGI Takeshi Fukuoka University, School of Medicine, Professor, 医学部, 教授 (40004717)
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| Co-Investigator(Kenkyū-buntansha) |
IWAMOTO Takahiro Fukuoka University, School of Medicine, Lecturer, 医学部, 講師 (20300973)
MIGITA Keisuke Fukuoka university, School of Medicine, Research Associate, 医学部, 助手 (10352262)
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| Project Period (FY) |
2005 – 2006
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| Keywords | ATP release mechanism / bradykinin / caffeine / endoplasmic reticulum / mitochondria / Ca^<2+>-signaling / ATP transporter |
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| Research Abstract |
In recent years, ATP is well-known to be served as a modulator of cellular functions via P2X and P2Y purinoceptors. However, so far, the mechanisms underlying the extracellular release of ATP and the related Ca^<2+>-signaling. remains unclear. The present subject was undertaken to clarify these points. The studies consist of separate parts as follows. First, in the study with cultured T. coli cells, bradykinin elicited ATP release mediated by B2 receptors, then, increased Ins(1,4,5)P3 production, triggering Ca^<2+>-release from endoplasmic reticulum. The Ca^<2+>-signal attains to the cell membrane and then, the membrane transporter, MRP1, will be activated. Finally, ATP is exported by MRP1 transporter. CFTR transporter and hemi channels were not involved in the export of ATP evoked by bradykinin.
In another study, it has been evaluated whether some Ca^<2+>-signaling contributes to the release of ATP evoked by bradykinin from cultured vas deferens smooth muscle cells. Bradykinin via RyR2 receptor elicits an increase of Ca^<2+> release from ER. The Ca^<2+> signaling was transferred to mitochondria (Mt) and, then, the elevation of Ca^<2+> levels in Mt activates the Ca^<2+>-dependent dehydrogenases and further the electron transfer system resulting in the enhancement of ATP synthesis in Mt. Finally, the ATP signals attain the cell membrane and the membranous ATP transport system is promoted. In conclusion, these findings suggest that the ATP export is triggered by the characteristic Ca^<2+> signaling from ER to MT.
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