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trans ‐Resveratrol inhibits calcium influx in thrombin‐stimulated human platelets
Author(s) -
Dobrydneva Yuliya,
Williams Roy L,
Blackmore Peter F
Publication year - 1999
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0702749
Subject(s) - resveratrol , platelet , chemistry , thrombin , thapsigargin , calcium , biochemistry , biophysics , intracellular , pharmacology , biology , immunology , organic chemistry
The phytoestrogenic compound trans ‐resveratrol ( trans ‐3,5,4′‐trihydroxystilbene) is found in appreciable quantities in grape skins and wine. It has been shown that both products rich in trans ‐resveratrol and pure trans ‐resveratrol inhibit platelet aggregation both in vivo and in vitro . However the mechanism of this action still remains unknown. An essential component of the aggregation process in platelets is an increase in intracellular free Ca 2+ ([Ca 2+ ] i ). Ca 2+ must enter the cell from the external media through specific and tightly regulated Ca 2+ channels in the plasma membrane. The objective of this study was to characterize what effect trans ‐resveratrol had on the Ca 2+ channels in thrombin stimulated platelets. In this study we showed that trans ‐resveratrol immediately inhibited Ca 2+ influx in thrombin‐stimulated platelets with an IC 50 of 0.5 μ M . trans ‐Resveratrol at 0.1, 1.0 and 10.0 μ M produced 20±6, 37±6 and 57±4% inhibition respectively of the effect of thrombin (0.01 u ml −1 ) to increase [Ca 2+ ] i .trans ‐Resveratrol also inhibited spontaneous Ba 2+ entry into Fura‐2 loaded platelets, with 0.1, 1.0 and 10.0 μ M trans ‐resveratrol producing 10±5, 30±5 and 50±7% inhibition respectively. This indicated that trans ‐resveratrol directly inhibited Ca 2+ channel activity in the platelets in the absence of agonist stimulation.trans ‐Resveratrol also inhibited thapsigargin‐mediated Ca 2+ influx into platelets. This suggests that the store‐operated Ca 2+ channels are one of the possible targets of trans ‐resveratrol. These channels rely on the emptying of the internal Ca 2+ stores to initiate influx of Ca 2+ into the cell. The phytoestrogens genistein, daidzein, apigenin and genistein‐glucoside (genistin) produced inhibitory effects against thrombin similar to those seen with trans ‐resveratrol. We conclude that trans ‐resveratrol is an inhibitor of store‐operated Ca 2+ channels in human platelets. This accounts for the ability of trans ‐resveratrol to inhibit platelet aggregation induced by thrombin.British Journal of Pharmacology (1999) 128 , 149–157; doi: 10.1038/sj.bjp.0702749