{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T11:41:17Z","timestamp":1768477277220,"version":"3.49.0"},"reference-count":32,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2002,1]]},"abstract":"<jats:p>\n            The immature megakaryoblastic cell line MEG-01 responds to iloprost with an increase in cytosolic Ca\n            <jats:sup>2+<\/jats:sup>\n            and cAMP. The Ca\n            <jats:sup>2+<\/jats:sup>\n            response is almost absent in CHRF-288-11 cells, but cAMP formation is preserved in this more mature megakaryoblastic cell line. Also, in human hematopoietic stem cells, iloprost induces a Ca\n            <jats:sup>2+<\/jats:sup>\n            response and cAMP formation. The Ca\n            <jats:sup>2+<\/jats:sup>\n            response is downregulated during megakaryocytopoiesis, but cAMP formation remains unchanged. The Ca\n            <jats:sup>2+<\/jats:sup>\n            increase may be caused by cAMP-mediated inhibition of Ca\n            <jats:sup>2+<\/jats:sup>\n            sequestration, because it is (1) independent of Ca\n            <jats:sup>2+<\/jats:sup>\n            entry; (2) mimicked by forskolin, an activator of adenylyl cyclase, and isobutylmethylxanthine, an inhibitor of phosphodiesterases; and (3) preserved in the presence of inhibitors of protein kinase A and inositol-1,4,5-triphosphate receptors. The small GTPase Rap1 has been implicated in the control of Ca\n            <jats:sup>2+<\/jats:sup>\n            sequestration. Indeed, Rap1 activation parallels the iloprost- and forskolin-induced Ca\n            <jats:sup>2+<\/jats:sup>\n            increase and is unaffected by the calcium chelator 1,2-bis(2-aminophenoxy)ethane-\n            <jats:italic>N<\/jats:italic>\n            ,\n            <jats:italic>N<\/jats:italic>\n            ,\n            <jats:italic>N<\/jats:italic>\n            \u2032,\n            <jats:italic>N<\/jats:italic>\n            \u2032,-tetraacetic acid-AM. These findings reveal a novel mechanism for elevating cytosolic Ca\n            <jats:sup>2+<\/jats:sup>\n            by cAMP, possibly via GTP-Rap1.\n          <\/jats:p>","DOI":"10.1161\/hq0102.101515","type":"journal-article","created":{"date-parts":[[2002,7,28]],"date-time":"2002-07-28T23:16:47Z","timestamp":1027898207000},"page":"179-186","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":14,"title":["Cyclic AMP Raises Intracellular Ca\n            <sup>2+<\/sup>\n            in Human Megakaryocytes Independent of Protein Kinase A"],"prefix":"10.1161","volume":"22","author":[{"given":"Els","family":"den Dekker","sequence":"first","affiliation":[{"name":"From the Thrombosis and Haemostasis Laboratory (E.d.D., G.G., H.v.d.V., J.D., C.K., J.-W.N.A.), Department of Haematology, University Medical Center Utrecht and Institute for Biomembranes, Utrecht University, Utrecht, and the Department of Biochemistry and Human Biology (J.W.M.H.), Maastricht University, Maastricht, The Netherlands, and the Department of Molecular Neurobiology (K.M.), Institute of Medical Science, Tokyo University, Tokyo, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johan W.M.","family":"Heemskerk","sequence":"additional","affiliation":[{"name":"From the Thrombosis and Haemostasis Laboratory (E.d.D., G.G., H.v.d.V., J.D., C.K., J.-W.N.A.), Department of Haematology, University Medical Center Utrecht and Institute for Biomembranes, Utrecht University, Utrecht, and the Department of Biochemistry and Human Biology (J.W.M.H.), Maastricht University, Maastricht, The Netherlands, and the Department of Molecular Neurobiology (K.M.), Institute of Medical Science, Tokyo University, Tokyo, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gertie","family":"Gorter","sequence":"additional","affiliation":[{"name":"From the Thrombosis and Haemostasis Laboratory (E.d.D., G.G., H.v.d.V., J.D., C.K., J.-W.N.A.), Department of Haematology, University Medical Center Utrecht and Institute for Biomembranes, Utrecht University, Utrecht, and the Department of Biochemistry and Human Biology (J.W.M.H.), Maastricht University, Maastricht, The Netherlands, and the Department of Molecular Neurobiology (K.M.), Institute of Medical Science, Tokyo University, Tokyo, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans","family":"van der Vuurst","sequence":"additional","affiliation":[{"name":"From the Thrombosis and Haemostasis Laboratory (E.d.D., G.G., H.v.d.V., J.D., C.K., J.-W.N.A.), Department of Haematology, University Medical Center Utrecht and Institute for Biomembranes, Utrecht University, Utrecht, and the Department of Biochemistry and Human Biology (J.W.M.H.), Maastricht University, Maastricht, The Netherlands, and the Department of Molecular Neurobiology (K.M.), Institute of Medical Science, Tokyo University, Tokyo, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jose\u0301","family":"Donath","sequence":"additional","affiliation":[{"name":"From the Thrombosis and Haemostasis Laboratory (E.d.D., G.G., H.v.d.V., J.D., C.K., J.-W.N.A.), Department of Haematology, University Medical Center Utrecht and Institute for Biomembranes, Utrecht University, Utrecht, and the Department of Biochemistry and Human Biology (J.W.M.H.), Maastricht University, Maastricht, The Netherlands, and the Department of Molecular Neurobiology (K.M.), Institute of Medical Science, Tokyo University, Tokyo, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Kroner","sequence":"additional","affiliation":[{"name":"From the Thrombosis and Haemostasis Laboratory (E.d.D., G.G., H.v.d.V., J.D., C.K., J.-W.N.A.), Department of Haematology, University Medical Center Utrecht and Institute for Biomembranes, Utrecht University, Utrecht, and the Department of Biochemistry and Human Biology (J.W.M.H.), Maastricht University, Maastricht, The Netherlands, and the Department of Molecular Neurobiology (K.M.), Institute of Medical Science, Tokyo University, Tokyo, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katsuhiko","family":"Mikoshiba","sequence":"additional","affiliation":[{"name":"From the Thrombosis and Haemostasis Laboratory (E.d.D., G.G., H.v.d.V., J.D., C.K., J.-W.N.A.), Department of Haematology, University Medical Center Utrecht and Institute for Biomembranes, Utrecht University, Utrecht, and the Department of Biochemistry and Human Biology (J.W.M.H.), Maastricht University, Maastricht, The Netherlands, and the Department of Molecular Neurobiology (K.M.), Institute of Medical Science, Tokyo University, Tokyo, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan-Willem N.","family":"Akkerman","sequence":"additional","affiliation":[{"name":"From the Thrombosis and Haemostasis Laboratory (E.d.D., G.G., H.v.d.V., J.D., C.K., J.-W.N.A.), Department of Haematology, University Medical Center Utrecht and Institute for Biomembranes, Utrecht University, Utrecht, and the Department of Biochemistry and Human Biology (J.W.M.H.), Maastricht University, Maastricht, The Netherlands, and the Department of Molecular Neurobiology (K.M.), Institute of Medical Science, Tokyo University, Tokyo, 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