Roles of myosin light-chain kinase in platelet shape change and aggregation.
We examined the roles of myosin light-chain kinase in platelet responses to ADP using wortmannin, which almost completely inhibited myosin light-chain kinase at 3-6 microM. This concentration of wortmannin did not affect ADP-induced changes in the shape of the platelets, but it markedly inhibited aggregation in platelet-rich plasma and washed platelets. ML-9, another inhibitor of myosin light chain kinase, elicited similar effects on the platelet responses to wortmannin. Electron microscopic studies showed that there was no wortmannin effect on the ADP-induced spheration of discoid platelets, pseudopod formation, or granule centralization. Wortmannin at concentrations which prevented myosin light-chain kinase also inhibited platelet aggregation induced by ADP in the presence of U46619, an analogue of thromboxane A2, which is a prerequisite for ADP-induced irreversible aggregation. Although wortmannin partially inhibited protein kinase C, the protein kinase C inhibitor Ro-31-7549 (5 microM) prevented neither ADP- or ADP/U46619-induced changes in the shape of the platelets nor aggregation. These results suggest that myosin light-chain kinase activation is a prerequisite for ADP-induced platelet aggregation, but not for changes in their shape.
Hashimoto
Y
Y
First Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Sasaki
H
H
Togo
M
M
Tsukamoto
K
K
Horie
Y
Y
Fukata
H
H
Watanabe
T
T
Kurokawa
K
K
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000730:Androstadienes / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D048429:Cell Size; D004789:Enzyme Activation; D006801:Humans; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors / Q000502:physiology*; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology*; D000077191:Wortmannin
D000730:Androstadienes; D000244:Adenosine Diphosphate; D009219:Myosin-Light-Chain Kinase; D000077191:Wortmannin