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Thromb Haemost 2001; 85(05): 882-889
DOI: 10.1055/s-0037-1615763
Review Article
Schattauer GmbH

Evidence for a Role for Phospholipase C, but not Phospholipase A2, in Platelet Activation in Response to Low Concentrations of Collagen

Leslie K. Lockhart
1   Departments of Oral Biology and Pharmacology & Therapeutics, University of Manitoba, Winnipeg, Manitoba, Canada, Present address: Hill Top Research, Inc., P.O. Box 429501, Cincinnati, OH 45242, USA
,
Caroline Pampolina
1   Departments of Oral Biology and Pharmacology & Therapeutics, University of Manitoba, Winnipeg, Manitoba, Canada, Present address: Hill Top Research, Inc., P.O. Box 429501, Cincinnati, OH 45242, USA
,
Brent R. Nickolaychuk
1   Departments of Oral Biology and Pharmacology & Therapeutics, University of Manitoba, Winnipeg, Manitoba, Canada, Present address: Hill Top Research, Inc., P.O. Box 429501, Cincinnati, OH 45242, USA
,
Archibald McNicol
1   Departments of Oral Biology and Pharmacology & Therapeutics, University of Manitoba, Winnipeg, Manitoba, Canada, Present address: Hill Top Research, Inc., P.O. Box 429501, Cincinnati, OH 45242, USA
› Author Affiliations
Further Information

Publication History

Received 11 September 2000

Accepted after resubmission 05 December 2000

Publication Date:
11 December 2017 (online)

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Summary

The release of arachidonic acid is a key component in platelet activation in response to low concentrations (1-20 g/ml) of collagen. The precise mechanism remains elusive although a variety of pathways have been implicated. In the present study the effects of inhibitors of several potentially key enzymes in these pathways have been examined. Collagen (1-10 g/ml) caused maximal platelet aggregation which was accompanied by the release of arachidonic acid, the synthesis of thromboxane A2, and p38MAPK phosphorylation. Preincubation with the dual cyclooxygenase/lipoxygenase inhibitor BW755C inhibited aggregation and thromboxane production, and reduced p38MAPK phosphorylation. A phospholipase C inhibitor, U73122, blocked collagen-induced aggregation and reduced arachidonic acid release, thromboxane synthesis and p38MAPK phosphorylation. Pretreatment with a cytosolic phospholipase A2 inhibitor, AACOCF3, blocked collagen-induced aggregation, reduced the levels of thromboxane formation and p38MAPK phosphorylation but had no significant effect on arachidonic acid release. In contrast inhibition of PKC by Rö31-8220 inhibited collagen-induced aggregation, did not affect p38MAPK phosphorylation but significantly potentiated arachidonic acid release and thromboxane formation. Collagen caused the tyrosine phosphorylation of phospholipase C 2 which was inhibited by pretreatment with U73122, unaffected by AACOCF3 and enhanced by Rö31-8220. These results suggest that cytosolic phospholipase A2 plays no role in the arachidonic acid release in response to collagen. In contrast, the data are consistent with phospholipase C 2 playing a role in an intricately controlled pathway, or multiple pathways, mediating the release of arachidonic acid in collagen-stimulated platelets.

Keywords

Platelets - collagen - arachidonic acid - phospholipase
 

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