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

Biochem Pharmacol. 1997 May 9;53(9):1257-62. doi: 10.1016/s0006-2952(96)00888-x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Platelets / drug effects*
  • Dose-Response Relationship, Drug
  • Enzyme Activation
  • Enzyme Inhibitors / pharmacology*
  • Estrenes / pharmacology*
  • Humans
  • Phospholipases A / metabolism*
  • Phospholipases A2
  • Platelet Aggregation Inhibitors / pharmacology*
  • Protein-Tyrosine Kinases / metabolism
  • Pyrrolidinones / pharmacology*
  • Thapsigargin / pharmacology
  • Thrombin / pharmacology

Substances

  • Enzyme Inhibitors
  • Estrenes
  • Platelet Aggregation Inhibitors
  • Pyrrolidinones
  • U 73343
  • Thapsigargin
  • Protein-Tyrosine Kinases
  • Phospholipases A
  • Phospholipases A2
  • Thrombin