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PMID: 7400315 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Phospholipid metabolism in stimulated human platelets. Changes in phosphatidylinositol, phosphatidic acid, and lysophospholipids.

The Journal of clinical investigation ·Vol. 66 ·No. 2 ·1980-08-00 ·Pages 275-83

Broekman MJ, Ward JW, Marcus AJ

Abstract

Endogenous phospholipid metabolism in stimulated human platelets was studied by phosphorus assay of major and minor components following separation by two-dimensional thin-layer chromatography. This procedure obviated the use of radioactive labels. Extensive changes were found in quantities of phosphatidylinositol (PI) and phosphatidic acid (PA) as a consequence of thrombin or collagen stimulation. Thrombin addition was followed by rapid alterations in the amount of endogenous PI and PA. The decrease in PI was not precisely reciprocated by an increase in PA when thrombin was the stimulus. This apparent discrepancy could be explained by removal of a transient intermediate in PI metabolism, such as diglyceride, formed by PI-specific phospholipase C (Rittenhouse-Simmons, S., J. Clin. Invest.63: 580-587, 1979). Diglyceride would be unavailable for PA formation by diglyceride kinase, if hydrolyzed by diglyceride lipase (Bell, R. L., D. A. Kennerly, N. Stanford, and P. W. Majerus. Proc. Natl. Acad. Sci. U. S. A.76: 3238-3241, 1979) to yield arachidonate for prostaglandin endoperoxide formation. Thrombin-treated platelets also accumulated lysophospho-glycerides. Specifically, lysophosphatidyl ethanolamines accumulated within 15s following thrombin addition. Fatty acid and aldehyde analysis indicated phospholipase A(2) activity, with an apparent preference for diacyl ethanolamine phosphoglycerides. In the case of collagen, these changes occurred concomitantly with aggregation and consumption of oxygen for prostaglandin endoperoxide formation.THESE STUDIES OF ENDOGENOUS PHOSPHOLIPID METABOLISM PROVIDE INFORMATION SUPPORTING THE EXISTENCE OF TWO PREVIOUSLY POSTULATED PATHWAYS FOR LIBERATION OF ARACHIDONIC ACID FROM PLATELET PHOSPHOLIPIDS: (a) the combined action of PI-specific phospholipase C plus diglyceride lipase yielding arachidonate derived from PI; and (b) a phospholipase A(2) acting primarily on diacyl ethanolamine phosphoglyceride.

MeSH Terms
Arachidonic Acids/blood Blood Platelets/metabolism Collagen/metabolism Fatty Acids/blood Humans Lysophosphatidylcholines/blood Phosphatidic Acids/blood Phosphatidylinositols/blood Phospholipases/blood Thrombin/metabolism
Chemicals
Arachidonic Acids Fatty Acids Lysophosphatidylcholines Phosphatidic Acids Phosphatidylinositols Collagen Phospholipases Thrombin
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Broekman M J
Ward J W
Marcus A J
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40 references, click to expand
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
Published
1980-08-00
Pages
275-83
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC371708
Subset
IM
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