2005 Fiscal Year Final Research Report Summary
Effect of lysophosphatidic acid in fluid flow-response in vascular endothelial cells
| Project/Area Number |
16590206
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
General pharmacology
|
|---|
| Research Institution | Showa University |
|---|
Principal Investigator |
OHATA Hisayuki Showa Univ., School of Pharmaceutical Sci., Assistant professor, 薬学部, 助教授 (00119166)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
YAMAMOTO Masayuki Showa Univ., School of Pharmaceutical Sci., Research assistant (90307067)
|
|---|
| Project Period (FY) |
2004 – 2005
|
| Keywords | mechanoreception / mechanosensitive channel / intracellular Ca^<2+> ion concentration / lysophosphatidic acid / lens epithelial cells / laser scanning confocal microscopy / in situ |
|---|
| 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.
|
Research Products
(10 results)
