Tetrandrine differentially inhibits aggregation and ATP-release of rat platelets.
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AIM: To examine the effects of tetrandrine (Tet) on the aggregation and ATP-release of rat washed platelets induced by several platelet activators. METHODS: Gel-filtration (Sepharose 2B) was used to isolate washed platelets from adult rats and the platelet aggragation and ATP-release were measured simultaneously. RESULTS: In the presence of Ca2+ 1 mmol.L-1, Tet 300 mumol.L-1 inhibited the aggregation induced by ADP (25 mumol.L-1), collagen (2.5 g.L-1), and thrombin (103 unit.L-1) by 62%, 60%, and 34%, respectively. It also inhibited arachidonic acid (1 mmol.L-1)-induced aggregation. Elevating intracellular Ca2+ concentration with the Ca2+ ionophore, calcimycin (30 mumol.L-1), or by blocking the intracellular calcium pump with cyclopiazonic acid (5 mumol.L-1) initiated platelet aggregation, which was also inhibited by Tet. In Ca(2+)-free medium, Tet still elicited an inhibitory effect on aggregation induced by ristocetin (2.5 g.L-1). Lower concentrations of Tet (30 nmol.L-1 to 3 mumol.L-1) failed to inhibit the aggregation (requiring Tet 10-300 mumol.L-1), but strongly suppressed ATP-release induced by ADP 10 mumol.L-1, both of which were measured simultaneously in a single sample. CONCLUSION: Tet elicits a nonselective inhibitory effect on platelet aggregation not solely due to its Ca2+ antagonism and may act on a final common pathway leading to platelet aggregation. Furthermore, Tet is a much potent inhibitor of the release of ATP in platelets.
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