Project/Area Number |
02670387
|
Research Category |
Grant-in-Aid for General Scientific Research (C)
|
Allocation Type | Single-year Grants |
Research Field |
Circulatory organs internal medicine
|
Research Institution | Tokyo Medical and Dental University |
Principal Investigator |
KISHI Yukio Tokyo Medical and Dental Univ., Dept. Medicine, Assistant, 医学部・第三内科, 助手 (70186211)
|
Project Period (FY) |
1990 – 1991
|
Project Status |
Completed (Fiscal Year 1991)
|
Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1991: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1990: ¥1,400,000 (Direct Cost: ¥1,400,000)
|
Keywords | Endothelial Cells / Cell Injury / Platelet / Cyclic Nucleotides / Phosphoinositide / Calcium / Adenine Nucleotides / Prostacyclin / 環境ヌクレオチド / アデニンヌクレオチド / グアニンヌクレオチド |
Research Abstract |
An in vitro study was performed to assess injury to vascular endothelial cells. Human platelets, activated by collagen, enhanced the leakage of radioactivity from cultured bovine aortic endothelial cells preloaded with[^3H]adenine ([^3H]adenine release). An analysis of radioactive materials by thin-layer chromatography revealed decreased intracellular ATP content in the cells treated with activated platelets. The medium contained AMP and adenosine, the latter increasing following the treatment of the cells. The[^3H]cyclic AMP showed time-dependent decrease in the prelabeled cells, exposed to the activated platelets. Moreover, activated platelets induced increase in inositol triphosphate- and cytosolic free calcium ion in the endothelial cells. The initial rapid increase in calcium concentration forming a spike was abolished when the activated platelets were pretreated with apyrase. Pretreatment of the endothelial cells with agents elevating the cyclic AMP levels prevented a [^3H]adenine release, while nifedipine or agents which produce effects that increase cyclic GMP levels had little effects. We conclude that calcium ion plays an important role in vascular endothelial injury by activated platelets and agents elevating cyclic AMP may protect the cells from injury by enhancing calcium sequestration.
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