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Carrageenan‐induced activation of human platelets is dependent on the phospholipase C Pathway
Author(s) -
Hatmi Mohamed,
Randon Jacques,
Faili Ahmad,
Vargaftig B. Boris
Publication year - 1993
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1993.tb08282.x
Subject(s) - chemistry , platelet , phospholipase c , phospholipase , carrageenan , platelet activating factor , phosphatidylinositol , phospholipase a2 , platelet activation , biochemistry , pharmacology , inositol phosphate , inositol , endocrinology , medicine , enzyme , biology , receptor , signal transduction
Stimulation of washed human platelets by the pro‐inflammatory polysaccharide carrageenan is accompanied by shape change, aggregation and release of granule contents and unaccompanied by thromboxane A 2 synthesis. Carrageenan triggers platelet activation through a prostaglandin synthetase‐independent mechanism. The phospholipase A 2 (PLA 2 ) inhibitor, p‐bromophenacyl bromide suppresses platelet responses to carrageenan (Vargaftig et al , 1980) probably by mechanism (s) other than those which involve PLA 2 activity. Exposure of platelets to carrageenan (2–25 μg/ml) induced inositol phosphate formation in a time‐ and concentration‐dependent manner, the level of inositol phosphate formation correllating with the intensity of aggregation. Neomycin, an aminoglycoside antibiotic which inhibits the phospholipase C ‐mediated phosphatidylinositol 4,5‐bisphosphate breakdown, suppressed both platelet activation and inositol phosphate formation. Inhibition was concentration‐dependent with an IC 50 value of about 180 μM. Platelet‐activating factor (PAF) is not responsible for carrageenan‐induced platelet activation and inositol phosphate formation, since exposure of platelets to carrageenan (25 μg/ ml) in the presence of compound WEB 2086 (100 μM). a PAF antagonist, failed to inhibit carrageenan responses. However, compound Ro 19‐3704, a structurally related antagonist of PAF reported to be also an inhibitor of phospholipases A 2 and C, inhibited concentration‐dependently (0.1–10 μg/ml). These findings indicate that carrageenan activates human platelets through a phospholipase C‐dependent mechanism and show that neomycin, at low concentrations, can be a selective inhibitor of phospholipase C‐mediated PIP2‐breakdown.