{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T10:51:10Z","timestamp":1791283870216,"version":"4.1.0"},"reference-count":39,"publisher":"American Society of Hematology","issue":"12","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2001,6,15]]},"abstract":"<jats:p>Sickling-induced cation fluxes contribute to cellular dehydration of sickle red blood cells (SS RBCs), which in turn potentiates sickling. This study examined the inhibition by dipyridamole of the sickling-induced fluxes of Na+, K+, and Ca++ in vitro. At 2% hematocrit, 10 \u03bcM dipyridamole inhibited 65% of the increase in net fluxes of Na+ and K+ produced by deoxygenation of SS RBCs. Sickle-induced Ca++ influx, assayed as 45Ca++uptake in quin-2\u2013loaded SS RBCs, was also partially blocked by dipyridamole, with a dose response similar to that of Na+and K+ fluxes. In addition, dipyridamole inhibited the Ca++-activated K+ flux (via the Gardos pathway) in SS RBCs, measured as net K+ efflux in oxygenated cells exposed to ionophore A23187 in the presence of external Ca++, but this effect resulted from reduced anion conductance, rather than from a direct effect on the K+channel. The degree of inhibition of sickling-induced fluxes was dependent on hematocrit, and up to 30% of dipyridamole was bound to RBC membranes at 2% hematocrit. RBC membrane content of dipyridamole was measured fluorometrically and correlated with sickling-induced flux inhibition at various concentrations of drug. Membrane drug content in patients taking dipyridamole for other clinical indications was similar to that producing inhibition of sickling-induced fluxes in vitro. These data suggest that dipyridamole might inhibit sickling-induced fluxes of Na+, K+, and Ca++ in vivo and therefore have potential as a pharmacological agent to reduce SS RBC dehydration.<\/jats:p>","DOI":"10.1182\/blood.v97.12.3976","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T12:46:47Z","timestamp":1027774007000},"page":"3976-3983","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":32,"title":["Dipyridamole inhibits sickling-induced cation fluxes in sickle red blood cells"],"prefix":"10.1182","volume":"97","author":[{"given":"Clinton H.","family":"Joiner","sequence":"first","affiliation":[{"name":"From the Cincinnati Comprehensive Sickle Cell Center and the Divisions of Pediatric and Medical Hematology\/Oncology, University of Cincinnati College of Medicine, Cincinnati, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maorong","family":"Jiang","sequence":"additional","affiliation":[{"name":"From the Cincinnati Comprehensive Sickle Cell Center and the Divisions of Pediatric and Medical Hematology\/Oncology, University of Cincinnati College of Medicine, Cincinnati, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William J.","family":"Claussen","sequence":"additional","affiliation":[{"name":"From the Cincinnati Comprehensive Sickle Cell Center and the Divisions of Pediatric and Medical Hematology\/Oncology, University of Cincinnati College of Medicine, Cincinnati, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy J.","family":"Roszell","sequence":"additional","affiliation":[{"name":"From the Cincinnati Comprehensive Sickle Cell Center and the Divisions of Pediatric and Medical Hematology\/Oncology, University of Cincinnati College of Medicine, Cincinnati, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahida","family":"Yasin","sequence":"additional","affiliation":[{"name":"From the Cincinnati Comprehensive Sickle Cell Center and the Divisions of Pediatric and Medical Hematology\/Oncology, University of Cincinnati College of Medicine, Cincinnati, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert S.","family":"Franco","sequence":"additional","affiliation":[{"name":"From the Cincinnati Comprehensive Sickle Cell Center and the Divisions of Pediatric and Medical Hematology\/Oncology, University of Cincinnati College of Medicine, Cincinnati, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"key":"2020021221124852100_B1","first-page":"68","article-title":"Sickling in vitro of reticulocytes from patients with sickle cell disease at venous oxygen tension.","volume":"24","author":"Horiuchi","year":"1998","journal-title":"Exp 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