摘要
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 μmol·L -1 inhibited the aggregation induced by ADP ( 25 μmol · 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 μmol · L-1), or by blocking the intracellular calcium pump with cyclopiazonic acid (5 μmol · L-1) initiated platelet aggregation, which was also inhibited by Tet. In Ca2+ -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
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 μmol·L -1 inhibited the aggregation induced by ADP ( 25 μmol · 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 μmol · L-1), or by blocking the intracellular calcium pump with cyclopiazonic acid (5 μmol · L-1) initiated platelet aggregation, which was also inhibited by Tet. In Ca2+ -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 μmol·L-1) failed to inhibit the aggregation (requiring Tet 10 - 300 μmol·L-1), but strongly suppressed ATP-release induced by ADP 10 μmol·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.
出处
《中国药理学报》
CSCD
1996年第2期105-108,共4页
Acta Pharmacologica Sinica
基金
Supported by grants from the CRCG of the University of Hong Kong
Hong Kong Research Grant Council.
