Tetrandrine differentially inhibits aggregation and ATP-release of rat platelets
Chen, Y.Y.; Kwan, C.Y.; Hui, S.C.
Zhongguo Yao Li Xue Bao 17(2): 105-108
1996
ISSN/ISBN: 0253-9756 PMID: 9772654 Document Number: 458108
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 aggregation and ATP-release were measured simultaneously. RESULTS: In the presence of Ca-2+ 1 mmol cntdot L-1, Tet 300 mu-mol cntdot L-1 inhibited the aggregation induced by ADP (25 mu-mol cntdot L-1), collagen (2. 5 g cntdot L-1), and thrombin ( 103 unit cntdot L-1) by 62 %, 60%, and 34 %, respectively. It also inhibited arachidonic acid ( 1 mmol cntdot L-1) - induced aggregation. Elevating intracellular Ca-2+ concentration with the Ca-2+ ionophore, calcimycin (30 mu-mol cntdot L-1), or by blocking the intracellular calcium pump with cyclopiazonic acid (5 mu-mol cntdot 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 cntdot L-1). Lower concentrations of Tet (30 nmol cntdot L-1 to 3 mu-mol cntdot L-1 ) failed to inhibit the aggregation ( requiring Tet 10-300 mu-mol cntdot L-1), but strongly suppressed ATP-release induced by ADP 10 mu-mol cntdot 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 Ca-2+ 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.