[The effect of triphenyltin fluoride on aggregation, ATP secretion and malondialdehyde formation of rabbit platelets in vitro].
Recent studies have demonstrated that triphenyltin fluoride (TPTF), widely used as an agricultural chemical and a marine antifoulant, inhibits collagen-induced platelet aggregation and ATP secretion in rabbits ex vivo. The aim of the present investigation was to elucidate the mechanism of the inhibitory action of TPTF by investigating platelet malondialdehyde (MDA) formation, aggregation and ATP secretion following the stimulation by various stimuli of rabbit platelets treated in vitro with TPTF, other triphenyl metals and aspirin. Although no inhibitory effect of TPTF was found on sodium arachidonate-induced platelet aggregation and ATP secretion, TPTF inhibited dose-dependently both platelet aggregation and ATP secretion induced by collagen. The antiaggregating (IC50) concentration of TPTF was 6.0 X 10(-6) M against collagen. In addition, TPTF prevented the collagen-, and thrombin-induced formation of MDA, but had little inhibitory effect on the conversion of exogenous arachidonic acid to MDA in platelets. In contrast, aspirin (10(-3) M) inhibited platelet aggregation, ATP secretion and MDA formation induced by all the stimuli tested. Other triphenyl metals did not any inhibitory effect on collagen-, and sodium arachidonate-induced platelet aggregation and ATP secretion even at a final concentration at 10(-3) M. These results suggest that TPTF has a specific inhibitory effect on platelet aggregation and ATP secretion by acting at some step(s) of platelet membrane between the binding site of collagen and thrombin and the release of arachidonic acid.
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001095:Arachidonic Acids / Q000037:antagonists & inhibitors; D001792:Blood Platelets / Q000378:metabolism*; D002478:Cells, Cultured; D003094:Collagen / Q000037:antagonists & inhibitors; D008297:Male; D008314:Malonates / Q000096:biosynthesis*; D008315:Malondialdehyde / Q000096:biosynthesis*; D009947:Organotin Compounds / Q000633:toxicity*; D010974:Platelet Aggregation / Q000187:drug effects*; D011817:Rabbits; D013997:Time Factors
D001095:Arachidonic Acids; D008314:Malonates; D009947:Organotin Compounds; C033303:triphenyltin fluoride; D008315:Malondialdehyde; D000255:Adenosine Triphosphate; D003094:Collagen