Dipyridamole inhibits sickling-induced cation fluxes in sickle red blood cells
| Autor: | Maorong Jiang, Nancy J. Roszell, Zahida Yasin, Clinton H. Joiner, Robert S. Franco, William J. Claussen |
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| Rok vydání: | 2001 |
| Předmět: |
Erythrocytes
Sodium Immunology Ionophore chemistry.chemical_element Anemia Sickle Cell Hematocrit Calcium Biochemistry Cations medicine Humans Cells Cultured Dose-Response Relationship Drug medicine.diagnostic_test Chemistry Biological activity Dipyridamole Cell Biology Hematology Red blood cell Spectrometry Fluorescence medicine.anatomical_structure Mechanism of action Potassium Biophysics medicine.symptom medicine.drug |
| Zdroj: | Blood. 97:3976-3983 |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | 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 microM 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 (45)Ca(++) uptake in quin-2-loaded 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. (Blood. 2001;97:3976-3983) |
| Databáze: | OpenAIRE |
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