Abstract
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-γ), the stable thromboxane mimetic U46619 (via PLC-β), 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.
Footnotes
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Send reprint requests to: Dr. A. McNicol, Departments of Oral Biology and Pharmacology & Therapeutics, University of Manitoba, 780 Bannatyne Avenue, Winnipeg, Manitoba, R3E 0W2, Canada. E-mail: mcnicol{at}ms.umanitoba.ca
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↵1 This study was funded in part by grants from the Heart and Stroke Foundation of Canada and the University of Manitoba.
- Abbreviations:
- PLC
- phospholipase C
- PKC
- protein kinase C
- PMA
- phorbol myristate acetate
- Tx
- thromboxane
- DAG
- 1,2-diacylglycerol
- IP3
- inositol 1,4,5 trisphosphate
- PRP
- platelet-rich plasma
- ACD
- acid citrate dextrose
- Received August 19, 1998.
- Accepted December 21, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
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