Anisomycin does not activate p38MAPK in human platelets.
Human platelets are known to contain three forms of mitogen-activated protein kinases; erk1, erk2, and p38MAPK. However the role(s) of mitogen-activated protein kinase cascades in platelet function remains to be determined. Evidence has been presented that suggests that these kinases are involved in the cytoskeleton and in the activation of phospholipase A2; however, other functions seem likely. The object of the present study was to examine the role of the p38MAPK in platelet function using anisomycin, a reported activator of p38MAPK, and SB203580, an inhibitor of p38MAPK. Thrombin and collagen caused the phosphorylation of p38MAPK and this was inhibited by SB203580. Anisomycin did not cause the aggregation of either intact or saponin-permeabilised platelets. In addition anisomycin failed to produce synergistic aggregation responses with submaximal concentrations of collagen, thrombin, the thromboxane mimetic U46619, or the calcium ionophore A23187. There was no detectable phosphorylation of p38MAPK in either intact platelets or platelet lysates incubated with anisomycin. Anisomycin also failed to modulate p38MAPK phosphorylation in response to submaximal concentrations of collagen, thrombin, U46619, or A23187. In contrast anisomycin did cause p38MAPK phosphorylation in rabbit lung and C3 fibroblasts and in rabbit lung fibroblast lysates. These data demonstrate that anisomycin has no detectable effect on either platelet function or p38MAPK phosphorylation and, therefore, that anisomycin has proven to be an ineffective tool to define the role that p38MAPK plays in platelet function.
Pampolina
C
C
Department of Oral Biology, University of Manitoba, Winnipeg, Canada.
McNicol
A
A
D000818:Animals; D000841:Anisomycin / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology*; D003094:Collagen / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D011817:Rabbits; D013917:Thrombin / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases
D004791:Enzyme Inhibitors; D007093:Imidazoles; D011725:Pyridines; D000841:Anisomycin; D003094:Collagen; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D013917:Thrombin; C093642:SB 203580