| Project/Area Number |
12670978
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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 |
Hematology
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| Research Institution | Niigata University |
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Principal Investigator |
FUSE Ichiro Niigata University, Medical Hospital, Associate professor, 医学部・附属病院, 助教授 (90242429)
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| Co-Investigator(Kenkyū-buntansha) |
TOBA Ken Niigata University, Medical Hospital, Lecturer, 医学部・附属病院, 講師 (60313540)
FURUKAWA Tatsuo Niigata University, Medical Hospital, Associate professor, 医学部・附属病院, 助教授 (00272849)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | platelet dysfunction / thromboxane A2 / thromboxane receptor / signal transduction |
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| Research Abstract |
We already clarified that the Arg^<60> to Leu mutation in the first cytoplasmic loop of the thromboxane _2j (TXA_2) receptor causes a bleeding disorder characterized by platelet unresponsiveness to TXA_2. However, we found other causes of this type of bleeding disorder. The patients had mild to moderate bleeding tendencies, and their platelet aggregation and secretion induced by ADP, collagen, arachidonic acid, stable tyhromboxane A2 and Ca ionophore A23187 was defective or much reduced. The analysis of second messenger formation showed that the inositol 1, 4, 5-triphosphate formation or Ca mobilization induced by thrombin, STA2 or A23187 was normal. Furhtermore, the phosphorylation of 47 K Da protein (pleckstrin) and 20 K Da protein (myosin light chain, MLC) in response to those agonists was normal.
These findings suggest that the defective site in the patients' platelets lies in the process distal to or independent of protein kinase C activation, Ca mobilization and MLC phosphorylation.
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