The Tyrosine Kinase Inhibitors, Genistein and Methyl 2,5-Dihydroxycinnamate, Inhibit the Release of (3H)Arachidonate from Human Platelets Stimulated by Thrombin or Collagen

Philip G Hargreaves; Ellen F Licking; Paul Sargeant; Stewart O Sage; Michael J Barnes; Richard W Farndale

doi:10.1055/s-0038-1648927

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1994; 72(04): 634-642
DOI: 10.1055/s-0038-1648927

Original Article

Schattauer GmbH Stuttgart

The Tyrosine Kinase Inhibitors, Genistein and Methyl 2,5-Dihydroxycinnamate, Inhibit the Release of (³H)Arachidonate from Human Platelets Stimulated by Thrombin or Collagen

Philip G Hargreaves

¹The Dept. of Biochemistry, University of Cambridge, Cambridge, UK

,

Ellen F Licking

¹The Dept. of Biochemistry, University of Cambridge, Cambridge, UK

,

Paul Sargeant

²The Physiological Laboratory, University of Cambridge, Cambridge, UK

,

Stewart O Sage

²The Physiological Laboratory, University of Cambridge, Cambridge, UK

,

Michael J Barnes

³Strangeways Research Laboratory, Cambridge, UK

,

Richard W Farndale

¹The Dept. of Biochemistry, University of Cambridge, Cambridge, UK

› Author Affiliations

Abstract

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Summary

We have investigated the effects of the tyrosine kinase inhibitors, genistein and methyl 2,5-dihydroxycinnamate, on [3H]arachidonic acid release from human platelets. Both tyrosine kinase inhibitors blocked, in a dose-dependent manner, the release of arachidonic acid stimulated by thrombin or suspensions of collagen fibres. Blockade by the tyrosine kinase inhibitors occurred early in the arachidonate release time course. Both genistein and methyl 2,5-dihydroxycinnamate also inhibited tyrosine phosphorylation in platelets. The inhibitors were specific in that they did not affect protein kinase C activity, ATP levels or mobilization of Ca2+ from internal stores. These findings suggest a role for tyrosine kinase activity in the regulation of phospholipase A2 in platelets stimulated by the physiological ligands, thrombin and collagen

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References

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