{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T06:35:42Z","timestamp":1790145342940,"version":"4.0.1"},"reference-count":28,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2001,12,20]],"date-time":"2001-12-20T00:00:00Z","timestamp":1008806400000},"content-version":"vor","delay-in-days":66,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["European Journal of Biochemistry"],"published-print":{"date-parts":[[2001,10,15]]},"abstract":"<jats:p>We have investigated the role of secretion and intracellular signalling events in aggregation induced by the glycoprotein (GP)VI\u2010selective snake venom toxin convulxin and by collagen. We demonstrate that aggregation induced by threshold concentrations of convulxin undergoes synergy with ADP acting via the P2Y<jats:sub>12<\/jats:sub> receptor whereas there is no synergy via the P2Y<jats:sub>1<\/jats:sub> receptor or with thromboxanes. On the other hand, apyrase, the P2Y<jats:sub>12<\/jats:sub> receptor antagonist, AR\u2010C67085, and indomethacin only marginally inhibit aggregation induced by convulxin. In comparison, these inhibitors severely attenuate the response to collagen. In order to investigate whether the weak inhibitory action against convulxin is due to release of agonists other than ADP from dense granules, experiments were performed on murine platelets deficient in this organelle (<jats:italic>pearl<\/jats:italic> mice platelets). A slightly greater reduction in aggregation induced by convulxin was observed in <jats:italic>pearl<\/jats:italic> platelets than in the presence of inhibitors of ADP, but a maximal response was still attained. Importantly, inhibition of protein kinase\u2003C further reduced the response to convulxin in <jats:italic>pearl<\/jats:italic> platelets demonstrating a direct role for the kinase in aggregation. Chelation of intracellular Ca<jats:sup>2+<\/jats:sup> with 1,2\u2010bis(2\u2010aminophenoxy)ethane\u2010<jats:italic>N<\/jats:italic>,<jats:italic>N<\/jats:italic>,<jats:italic>N<\/jats:italic>,<jats:italic>N<\/jats:italic>\u2032,<jats:italic>N<\/jats:italic>\u2032\u2010tetraacetic acid (acetoxymethyl)ester (BAPTA\u2010AM) abolished aggregation induced by convulxin under all conditions. Activation of phospholipase\u2003C by convulxin was potentiated by ADP acting through the P2Y<jats:sub>12<\/jats:sub> receptor. In conclusion, we show that Ca<jats:sup>2+<\/jats:sup> and protein kinase\u2003C, but not release of the secondary agonists ADP and thromboxane A<jats:sub>2<\/jats:sub>, are required for full aggregation induced by convulxin, whereas the response induced by collagen shows a much greater dependence on secretion of secondary agonists.<\/jats:p>","DOI":"10.1046\/j.0014-2956.2001.02448.x","type":"journal-article","created":{"date-parts":[[2003,3,11]],"date-time":"2003-03-11T18:17:32Z","timestamp":1047406652000},"page":"5242-5248","source":"Crossref","is-referenced-by-count":48,"title":["Signalling events underlying platelet aggregation induced by the glycoprotein VI agonist convulxin"],"prefix":"10.1111","volume":"268","author":[{"given":"Ben T.","family":"Atkinson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret J.","family":"Stafford","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine J.","family":"Pears","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve P.","family":"Watson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2001,12,20]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI8944"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-5699(98)01267-5"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0037-1615855"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0037-1614427"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.4.2024"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.4.2030"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/09537100050129305"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI8399"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(98)00025-8"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/35051599"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.14.8070"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0037-1614384"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.41.29108"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(98)01049-7"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(99)01313-7"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1006\/mgme.1999.2891"},{"key":"e_1_2_7_18_1","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1182\/blood.V94.1.146.413k39_146_155","article-title":"Abnormal expression and subcellular distribution of subunit proteins of the AP\u20103 adaptor complex lead to platelet storage pool deficiency in the pearl mouse","volume":"94","author":"Zhen L.","year":"1999","journal-title":"Blood."},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0041-0101(97)00021-4"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.12.2793"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.30.18095"},{"key":"e_1_2_7_22_1","first-page":"866","article-title":"Rapid reactions of platelets studied by a quenched\u2010flow approach: aggregation kinetics","volume":"100","author":"Gear A.R.","year":"1982","journal-title":"J. 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