Spin label study of the effect of ticlopidine on platelets.

The effect of ticlopidine on platelet membrane fluidity was investigated using a spin label technique. Ticlopidine, when orally administered to rats, increased both the order parameter and the motion parameter, indicating a decrease in the membrane fluidity of platelets. On the other hand, the order parameter and the motion parameter decreased markedly when the platelets were aggregated by thrombin. Ticlopidine inhibited the thrombin-induced aggregation of platelets and caused a slight increase in order parameter and motion parameter in thrombin-aggregated platelets. Judging from sodium dodecyl sulfate polyacrylamide gel electrophoresis, ticlopidine did not modify the electrophoretic pattern of platelet proteins appreciably. Ticlopidine decreased cholesterol/phospholipids molar ratio and increased slightly total amounts of proteins of the platelets. These results indicate that the inhibitory action by ticlopidine was accompanied by changes in membrane fluidity, and these changes were due to a perturbation of the membrane phospholipid core of the platelets by ticlopidine and/or its metabolites.