This project is aimed at an understanding of the role of the metabolism of arachidonyl phospholipids in stimulus-response coupling in platelets. Intermediates and end products of the """"""""phosphatidyl inositol effect"""""""", of phospholipases A2 and C, and of cyclooxygnase and lipoxygenase will be measured. The rationale is that the major barrior to resolution of the cause-effect relationships of phospholipid metabolism/arachidonate oxygenation in the response of platelets to stimuli is in part because these processes are usually measured during the platelet response to the strongest agonists. Much of the metabolism is thus likely to be a consequence of full platelet activation rather than an expression of a regulatory or second messenger role. Furthermore, it is likely that different pathways (e.g. phospholipase A2 vs phospholipase C) will function under different regulatory demands. This will be analyzed by comparing metabolism in response to weak vs strong agonists, in response to weak agonists where aggregation-mediated activation is permitted or inhibited, and in response to agonists in the presence of various metabolic inhibitors. This should permit correlation of different pathways with specific physiological functions. Arachidonyl phospholipid metabolism will be followed by pre-labelling phospholipids with arachidonate, stearate, or glycerol and by measuring incorporation of 32P into phosphatidic acid. Metabolities will be separated by thin-layer chromatography and high performance liquid chromatography.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL017729-12
Application #
3335417
Study Section
(EH)
Project Start
1978-05-01
Project End
1988-04-30
Budget Start
1986-05-01
Budget End
1988-04-30
Support Year
12
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Suny Downstate Medical Center
Department
Type
Schools of Medicine
DUNS #
068552207
City
Brooklyn
State
NY
Country
United States
Zip Code
11203