| Project/Area Number |
16590206
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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 | Showa University |
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Principal Investigator |
OHATA Hisayuki Showa Univ., School of Pharmaceutical Sci., Assistant professor, 薬学部, 助教授 (00119166)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAMOTO Masayuki Showa Univ., School of Pharmaceutical Sci., Research assistant (90307067)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2004: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | mechanoreception / mechanosensitive channel / intracellular Ca^<2+> ion concentration / lysophosphatidic acid / lens epithelial cells / laser scanning confocal microscopy / in situ / リゾホスファチジン酸 |
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| Research Abstract |
In endothelial cells, mechanical stress may be essential for local hemodynamic control. Increase in intracellular Ca^<2+> concentration ([Ca^<2+>]_i) is an important signal for mechanoreception, however, the molecular mechanisms remain unclear. We demonstrated that lysophosphatidic acid (LPA, 0.3-10 μM), a bioactive phospholipid, sensitizes response of in intracellular Ca^<2+> concentration ([Ca^<2+>]_i) to mechanical stress in several cell types. The sensitizing effect of LPA was observed in mouse aorta and renal artery in situ. The increase in endothelial [Ca^<2+>]_i caused subsequent [Ca^<2+>]_i transients and contraction in smooth muscle cells in aorta. We then examined the mechanism of LPA-induced endothelium-dependent vascular contraction. Endothelial Ca^<2+> response and vascular contraction were observed with multi photon laser scanning microscopy. The vascular contraction induced by LPA was inhibited by SQ-29548, an antagonist of thromboxane A_2 (TXA2)/prostagrandin H_2 (PGH2) receptor. Moreover, this contraction was partly inhibited by OKY-046 (ozagrel), an inhibitor of TXA2 synthetase. These results suggest that LPA in the presence of fluid flow induced vascular contraction was regulated by endothelium-derived TXA2/PGH2. We also demonstrated that sensitizing effect of LPA in shear stress-dependent Ca^<2+> response has region-specific property in renal artery and is induced through other receptor than LPA-1,-2 and -3. We hypothesize that LPA acts as a mechanosensitizer in endothelial cells.
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