{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T16:10:54Z","timestamp":1792080654933,"version":"4.4.0"},"reference-count":39,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":3438,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[1999,9]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>The phytoestrogenic compound <jats:italic>trans<\/jats:italic>\u2010resveratrol (<jats:italic>trans<\/jats:italic>\u20103,5,4\u2032\u2010trihydroxystilbene) is found in appreciable quantities in grape skins and wine. It has been shown that both products rich in <jats:italic>trans<\/jats:italic>\u2010resveratrol and pure <jats:italic>trans<\/jats:italic>\u2010resveratrol inhibit platelet aggregation both <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic>. However the mechanism of this action still remains unknown.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>An essential component of the aggregation process in platelets is an increase in intracellular free Ca<jats:sup>2+<\/jats:sup> ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>). Ca<jats:sup>2+<\/jats:sup> must enter the cell from the external media through specific and tightly regulated Ca<jats:sup>2+<\/jats:sup> channels in the plasma membrane. The objective of this study was to characterize what effect <jats:italic>trans<\/jats:italic>\u2010resveratrol had on the Ca<jats:sup>2+<\/jats:sup> channels in thrombin stimulated platelets.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In this study we showed that <jats:italic>trans<\/jats:italic>\u2010resveratrol immediately inhibited Ca<jats:sup>2+<\/jats:sup> influx in thrombin\u2010stimulated platelets with an IC<jats:sub>50<\/jats:sub> of 0.5\u2003\u03bc<jats:sc>M<\/jats:sc>. <jats:italic>trans<\/jats:italic>\u2010Resveratrol at 0.1, 1.0 and 10.0\u2003\u03bc<jats:sc>M<\/jats:sc> produced 20\u00b16, 37\u00b16 and 57\u00b14% inhibition respectively of the effect of thrombin (0.01 u\u2003\u2003ml<jats:sup>\u22121<\/jats:sup>) to increase [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p><jats:italic>trans<\/jats:italic>\u2010Resveratrol also inhibited spontaneous Ba<jats:sup>2+<\/jats:sup> entry into Fura\u20102 loaded platelets, with 0.1, 1.0 and 10.0\u2003\u03bc<jats:sc>M<\/jats:sc> <jats:italic>trans<\/jats:italic>\u2010resveratrol producing 10\u00b15, 30\u00b15 and 50\u00b17% inhibition respectively. This indicated that <jats:italic>trans<\/jats:italic>\u2010resveratrol directly inhibited Ca<jats:sup>2+<\/jats:sup> channel activity in the platelets in the absence of agonist stimulation.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p><jats:italic>trans<\/jats:italic>\u2010Resveratrol also inhibited thapsigargin\u2010mediated Ca<jats:sup>2+<\/jats:sup> influx into platelets. This suggests that the store\u2010operated Ca<jats:sup>2+<\/jats:sup> channels are one of the possible targets of <jats:italic>trans<\/jats:italic>\u2010resveratrol. These channels rely on the emptying of the internal Ca<jats:sup>2+<\/jats:sup> stores to initiate influx of Ca<jats:sup>2+<\/jats:sup> into the cell.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The phytoestrogens genistein, daidzein, apigenin and genistein\u2010glucoside (genistin) produced inhibitory effects against thrombin similar to those seen with <jats:italic>trans<\/jats:italic>\u2010resveratrol.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We conclude that <jats:italic>trans<\/jats:italic>\u2010resveratrol is an inhibitor of store\u2010operated Ca<jats:sup>2+<\/jats:sup> channels in human platelets. This accounts for the ability of <jats:italic>trans<\/jats:italic>\u2010resveratrol to inhibit platelet aggregation induced by thrombin.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (1999) <jats:bold>128<\/jats:bold>, 149\u2013157; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0702749\">10.1038\/sj.bjp.0702749<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0702749","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T20:24:47Z","timestamp":1106943887000},"page":"149-157","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":78,"title":["<i>trans<\/i>\u2010Resveratrol inhibits calcium influx in thrombin\u2010stimulated human platelets"],"prefix":"10.1111","volume":"128","author":[{"given":"Yuliya","family":"Dobrydneva","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roy L","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter F","family":"Blackmore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(93)92188-Y"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)45614-1"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1997.sp021927"},{"key":"e_1_2_7_5_1","first-page":"1","article-title":"Antiplatelet activity of synthetic and natural resveratrol in red wine","volume":"17","author":"BERTELLI A.A.","year":"1995","journal-title":"Int. J. Tiss. React."},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2760(87)90082-8"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0049-3848(87)90070-3"},{"key":"e_1_2_7_8_1","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1016\/S0021-9258(19)40024-0","article-title":"Progesterone and 17 \u03b1\u2010hydroxyprogesterone: Novel stimulators of calcium influx in human sperm","volume":"265","author":"BLACKMORE P.F.","year":"1990","journal-title":"J. Biol. Chem."},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4615-2994-1_2"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0143-4160(96)90068-8"},{"key":"e_1_2_7_11_1","first-page":"89","volume-title":"Haemostasis and Thrombosis","author":"CRAWFORD N.","year":"1994"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.47.30855"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3835(98)00130-X"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.25.14138"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.3109\/09537109409006439"},{"key":"e_1_2_7_16_1","first-page":"31","volume-title":"Haemostasis and Thrombosis","author":"HEYNS A.","year":"1994"},{"key":"e_1_2_7_17_1","first-page":"243","article-title":"Pharmacological receptors on blood platelets","volume":"43","author":"HOURANI S.M.O.","year":"1991","journal-title":"Pharmacol. Rev."},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.275.5297.218"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1021\/np50100a021"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/67.5.867"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.3181\/00379727-208-43830"},{"key":"e_1_2_7_22_1","doi-asserted-by":"crossref","first-page":"2441","DOI":"10.1016\/S0021-9258(19)39818-7","article-title":"Thrombin stimulates the production of a novel polyphosphoinositide in human platelets","volume":"265","author":"NOLAN R.D.","year":"1990","journal-title":"J. Biol. Chem."},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0143-4160(92)90026-O"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/0009-8981(95)06045-1"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/0009-8981(96)06236-5"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1997.77.4.901"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0701784"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2760(95)00224-3"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.1.175"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.1997.sp004066"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ph.52.030190.002243"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/0143-4160(92)90035-Q"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(93)81172-V"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)46823-2"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9120(96)00155-5"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.83.7.2223"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.7.2466"},{"key":"e_1_2_7_38_1","first-page":"49","volume-title":"Haemostasis and Thrombosis","author":"WHITE J.G.","year":"1994"},{"key":"e_1_2_7_39_1","first-page":"14","article-title":"Recent phytoestrogen research","volume":"1","author":"WILLIAMS R.L.","year":"1998","journal-title":"Chem. Industry"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/334703a0"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fsj.bjp.0702749","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fsj.bjp.0702749","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1038\/sj.bjp.0702749","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,29]],"date-time":"2023-10-29T12:57:35Z","timestamp":1698584255000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1038\/sj.bjp.0702749"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,9]]},"references-count":39,"journal-issue":{"issue":"1","published-print":{"date-parts":[[1999,9]]}},"alternative-id":["10.1038\/sj.bjp.0702749"],"URL":"https:\/\/doi.org\/10.1038\/sj.bjp.0702749","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999,9]]},"assertion":[{"value":"2009-01-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}