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 microM) inhibited the platelet aggregation and adenosine triphosphate release induced by arachidonic acid (100 microM), collagen (10 microg/mL), or thrombin (0.1 U/mL) in a dose-dependent manner. The thromboxane B2 formation caused by collagen or thrombin was inhibited by dantrolene, while formation of thromboxane B2 and prostaglandin D2 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 microM). 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.
Chou
T C
TC
Graduate Institute of Medical Sciences, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC. tcchou@ms5.hinet.net
Li
C Y
CY
D000255:Adenosine Triphosphate / Q000097:blood / Q000378:metabolism; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D000242:Cyclic AMP / Q000097:blood; D003620:Dantrolene / Q000494:pharmacology*; D009125:Muscle Relaxants, Central / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000097:blood / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects*; D015230:Prostaglandin D2 / Q000097:blood; D011817:Rabbits; D013929:Thromboxane B2 / Q000097:blood
D009125:Muscle Relaxants, Central; D010716:Phosphatidylinositols; D013929:Thromboxane B2; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D003620:Dantrolene; D015230:Prostaglandin D2