Inhibitory mechanisms of dantrolene on platelet aggregation

The antiplatelet effect of dantrolene and possible inhibitory mechanisms were studied in rabbit platelets. Preincubation of rabbit washed platelets with dantrolene (50-300 mu M) inhibited the platelet aggregation and adenosine triphosphate release induced by arachidonic acid (100 mu M), collagen (10 mu g/mL), or thrombin (0.1 U/mL) in a dose-dependent manner. The thromboxane B-2 formation caused by collagen or thrombin was inhibited by dantrolene, while formation of thromboxane B-2 and prostaglandin D-2 induced by arachidonic acid were not inhibited. In addition, the formation of phosphoinositide breakdown and the rise of intracellular calcium level induced by collagen or thrombin were also inhibited in a dose-dependent manner by dantrolene in the presence of indomethacin (2 mu M). However, the platelets cyclic AMP level was not affected by dantrolene, In conclusion, the present study demonstrates that dantrolene inhibits platelet activation mainly due to suppression of phosphoinositide breakdown. (C) 1999 Elsevier Science Ltd. All rights reserved.