Human platelet activation is inhibited upstream of the activation of phospholipase A2 by U73343.

J.W.M. Heemskerk; M.A.H. Feijge; S.O. Sage; R.W. Farndale

doi:10.1016/S0006-2952(96)00888-X

Human platelet activation is inhibited upstream of the activation of phospholipase A2 by U73343.

J.W.M. Heemskerk, M.A.H. Feijge, S.O. Sage, R.W. Farndale

NUTRIM School of Nutrition and Translational Research in Metabolism

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Department of Human Biology, University of Limburg, Maastricht, The Netherlands.

U73122 is known as an inhibitor of phospholipase C (PLC; EC 3.1.4.11). Its close structural analogue, U73343, lacks this activity and is used as a control compound. We have found that both compounds interfere with platelet signal transduction. U73122 completely abolished aggregation evoked by thrombin, TG, and collagen. Aggregation evoked by TG and collagen was also blocked by U73343, an effect due to inhibition of TxA2 production. U73343 was a potent inhibitor of TG-evoked arachidonic acid release, but a weak inhibitor of cytosolic phospholipase A2 (cPLA2; EC 3.1.1.4) activity. Cytosolic PLA2 activation in platelets involves protein tyrosine phosphorylation. U73343 inhibited TG- and collagen-evoked protein tyrosine phosphorylation, which can thus explain its action against these agents. These data indicate that caution is needed when using U73343 along with U73122 in the study of intracellular signalling pathways.

Original language	English
Pages (from-to)	1257-1262
Number of pages	6
Journal	Biochemical Pharmacology
Volume	53
Issue number	9
DOIs	https://doi.org/10.1016/S0006-2952(96)00888-X
Publication status	Published - 1 Jan 1997

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10.1016/S0006-2952(96)00888-X

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title = "Human platelet activation is inhibited upstream of the activation of phospholipase A2 by U73343.",

abstract = "Department of Human Biology, University of Limburg, Maastricht, The Netherlands.U73122 is known as an inhibitor of phospholipase C (PLC; EC 3.1.4.11). Its close structural analogue, U73343, lacks this activity and is used as a control compound. We have found that both compounds interfere with platelet signal transduction. U73122 completely abolished aggregation evoked by thrombin, TG, and collagen. Aggregation evoked by TG and collagen was also blocked by U73343, an effect due to inhibition of TxA2 production. U73343 was a potent inhibitor of TG-evoked arachidonic acid release, but a weak inhibitor of cytosolic phospholipase A2 (cPLA2; EC 3.1.1.4) activity. Cytosolic PLA2 activation in platelets involves protein tyrosine phosphorylation. U73343 inhibited TG- and collagen-evoked protein tyrosine phosphorylation, which can thus explain its action against these agents. These data indicate that caution is needed when using U73343 along with U73122 in the study of intracellular signalling pathways.",

author = "J.W.M. Heemskerk and M.A.H. Feijge and S.O. Sage and R.W. Farndale",

year = "1997",

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T1 - Human platelet activation is inhibited upstream of the activation of phospholipase A2 by U73343.

AU - Heemskerk, J.W.M.

AU - Feijge, M.A.H.

AU - Sage, S.O.

AU - Farndale, R.W.

PY - 1997/1/1

Y1 - 1997/1/1

N2 - Department of Human Biology, University of Limburg, Maastricht, The Netherlands.U73122 is known as an inhibitor of phospholipase C (PLC; EC 3.1.4.11). Its close structural analogue, U73343, lacks this activity and is used as a control compound. We have found that both compounds interfere with platelet signal transduction. U73122 completely abolished aggregation evoked by thrombin, TG, and collagen. Aggregation evoked by TG and collagen was also blocked by U73343, an effect due to inhibition of TxA2 production. U73343 was a potent inhibitor of TG-evoked arachidonic acid release, but a weak inhibitor of cytosolic phospholipase A2 (cPLA2; EC 3.1.1.4) activity. Cytosolic PLA2 activation in platelets involves protein tyrosine phosphorylation. U73343 inhibited TG- and collagen-evoked protein tyrosine phosphorylation, which can thus explain its action against these agents. These data indicate that caution is needed when using U73343 along with U73122 in the study of intracellular signalling pathways.

AB - Department of Human Biology, University of Limburg, Maastricht, The Netherlands.U73122 is known as an inhibitor of phospholipase C (PLC; EC 3.1.4.11). Its close structural analogue, U73343, lacks this activity and is used as a control compound. We have found that both compounds interfere with platelet signal transduction. U73122 completely abolished aggregation evoked by thrombin, TG, and collagen. Aggregation evoked by TG and collagen was also blocked by U73343, an effect due to inhibition of TxA2 production. U73343 was a potent inhibitor of TG-evoked arachidonic acid release, but a weak inhibitor of cytosolic phospholipase A2 (cPLA2; EC 3.1.1.4) activity. Cytosolic PLA2 activation in platelets involves protein tyrosine phosphorylation. U73343 inhibited TG- and collagen-evoked protein tyrosine phosphorylation, which can thus explain its action against these agents. These data indicate that caution is needed when using U73343 along with U73122 in the study of intracellular signalling pathways.

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DO - 10.1016/S0006-2952(96)00888-X

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