Details

Autor(en) / Beteiligte

• Joiner, Clinton H.
• Jiang, Maorong
• Claussen, William J.
• Roszell, Nancy J.
• Yasin, Zahida
• Franco, Robert S.

Titel

Dipyridamole inhibits sickling-induced cation fluxes in sickle red blood cells

Ist Teil von

• Blood, 2001-06, Vol.97 (12), p.3976-3983

Ort / Verlag

Washington, DC: Elsevier Inc

Erscheinungsjahr

2001

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 μM 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–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.