{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T21:56:12Z","timestamp":1787003772836,"version":"build-2736575974"},"reference-count":42,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2009,2,2]],"date-time":"2009-02-02T00:00:00Z","timestamp":1233532800000},"content-version":"vor","delay-in-days":2255,"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":[[2002,12]]},"abstract":"<jats:p>\n                    <jats:list list-type=\"explicit-label\">\n                      <jats:list-item>\n                        <jats:p>The mechanism(s) by which vascular endothelial growth factor (VEGF) induces endothelial nitric oxide synthase (eNOS) activation remain(s) unclear up to a certain extent. Therefore, we sought to evaluate the contribution of numerous pathways in VEGF\u2010induced nitric oxide (NO) synthesis by measuring cGMP production. In addition, as VEGF induces the synthesis of NO and platelet\u2010activating factor (PAF), we wanted to assess if the induction of PAF and NO is contributing to the synthesis of each other.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>\n                          Herein, we show that a treatment of endothelial cells with a phospholipase C (PLC) inhibitor (U73122), a calmodulin antagonist (W\u20107) or with intracellular calcium chelators (EGTA\/AM, BAPTA\/AM) prevented VEGF\u2010mediated eNOS Ser\n                          <jats:sup>1177<\/jats:sup>\n                          \u2010phosphorylation and NO synthesis measured by cGMP production.\n                        <\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>\n                          Pretreatment with phosphatidylinositol 3\u2010kinase (PI3K) (Wortmannin, LY294002) or protein kinase C (PKC) (GF109203X, Ro318220) inhibitors attenuated eNOS Ser\n                          <jats:sup>1177<\/jats:sup>\n                          \u2010phosphorylation mediated by VEGF, but did not alter immediate (0\u201310 min) cGMP synthesis induced by VEGF, but abrogated by up to 84% the delayed (10\u201330 min) cGMP synthesis.\n                        <\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>\n                          Pretreatment with PAF synthesis inhibitors or with PAF receptor antagonists did not abrogate neither eNOS Ser\n                          <jats:sup>1177<\/jats:sup>\n                          \u2010phosphorylation nor cGMP synthesis mediated by VEGF.\n                        <\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>\n                          In conclusion, VEGF induces an immediate cGMP synthesis through the PLC\u2010Ca\n                          <jats:sup>2+<\/jats:sup>\n                          \/CaM pathway, and that the induction of delayed cGMP synthesis implies Akt and PKC activity.\n                        <\/jats:p>\n                      <\/jats:list-item>\n                    <\/jats:list>\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:italic>British Journal of Pharmacology<\/jats:italic>\n                    (2002)\n                    <jats:bold>137<\/jats:bold>\n                    , 1021\u20131030. doi:\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0704956\">10.1038\/sj.bjp.0704956<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1038\/sj.bjp.0704956","type":"journal-article","created":{"date-parts":[[2002,11,12]],"date-time":"2002-11-12T13:47:25Z","timestamp":1037108845000},"page":"1021-1030","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":137,"title":["Immediate and delayed VEGF\u2010mediated NO synthesis in endothelial cells: Role of PI3K, PKC and PLC pathways"],"prefix":"10.1111","volume":"137","author":[{"given":"David S","family":"G\u00e9linas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal N","family":"Bernatchez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Rollin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas G","family":"Bazan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin G","family":"Sirois","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,2,2]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0704367"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.43.31047"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0704215"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1139\/y59-099"},{"key":"e_1_2_7_6_1","first-page":"213","article-title":"Tumor\u2010secreted vascular permeability factor increases cytosolic Ca2+ and von Willebrand factor release in human endothelial cells","volume":"138","author":"BROCK T.A.","year":"1991","journal-title":"Am. 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