The phospholipase C inhibitor U73122 inhibits phorbol ester-induced platelet activation

Departments of Pharmacology & Therapeutics and Oral Biology, University of Manitoba, Winnipeg, Manitoba, Canada.
Journal of Pharmacology and Experimental Therapeutics (Impact Factor: 3.97). 06/1999; 289(2):721-8.
Source: PubMed


Activation of phospholipase C (PLC) is a central component of the signal transduction process in numerous cells, including platelets. U73122 has been widely used as a selective PLC inhibitor. In the present study, the effects of U73122 on platelet function have been further examined. Platelets were stimulated with collagen (via PLC-gamma), the stable thromboxane mimetic U46619 (via PLC-beta), or phorbol myristate acetate (PMA) via protein kinase C (PKC). Consistent with inhibition of PLC, U73122 inhibited platelet aggregation and [3H]-serotonin release in response to collagen and U46619 in a concentration-dependent manner. Similarly, U73122 blocked collagen-induced release of thromboxane A2. U73122 also inhibited U46619-induced [32P]phosphatidic acid production and phosphorylation of the major PKC substrate, pleckstrin. U73122 had no effect on PMA-induced pleckstrin phosphorylation, [3H]-serotonin release, or intracellular vacuole formation. However, U73122 did inhibit PMA-induced platelet aggregation and fibrinogen binding. Overall, these results suggest that U73122, in addition to its inhibition of PLC, also affects PKC-independent events that interfere with platelet aggregation.

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    • "We next turned our attention to the signaling events occurring after the Frizzled receptor and especially the possible role of phospolipase C (PLC) signaling, which is known to be activated by Gβγ (Ahumada et al., 2002). Addition of a specific PLC inhibitor, u73122 (Lockhart and McNicol, 1999) to cells expressing β 2 AR/RFz1 or β 2 AR/RFz2 and induced with Iso prevented the loss of Dishevelled (Figure 5D). Because PLC involvement occurs after Gβγ and before Ca +2 /PKC the pathway involved in the downregulation of Dishevelled is expected to follow this order (Wnt/Frizzled→Gβγ→ PLC→Ca +2 /PKC signaling) (Figure 4C-E and 5D). "
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