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Deoxygenation-induced cation fluxes in sickle cells: II. Inhibition by
stilbene disulfonates
CH Joiner
Department of Pediatrics, University of Cincinnati, College of Medicine,
OH.
Deoxygenation-induced cation movements in sickle cells were inhibited 80%
to 85% by the anion transport inhibitor, 4,4'-diisothiocyano-
2,2'disulfostilbene (DIDS). Morphologic sickling was not altered by DIDS
treatment, demonstrating that morphologic sickling was not sufficient to
produce cation leaks in sickle cells. DIDS inhibition of
deoxygenation-induced cation flux was not affected when l- replaced Cl- ,
indicating that conductive anion movements did not limit cation flux in
deoxygenated cells treated with DIDS. Inhibition was irreversible after
preincubation with DIDS at 37 degrees C for 20 minutes, and was not
affected by the oxygenation state of cells at the time of drug exposure.
Sulfate self-exchange was inhibited at lower DIDS concentrations than was
deoxygenation-induced flux. Incubation of cells with DIDS at 4 degrees C
produced progressive blockade of sulfate exchange, but did not alter
deoxygenation-induced cation fluxes. Other stilbene disulfonates, including
compounds incapable of covalent reactions, also inhibited
deoxygenation-induced cation movements, although several other inhibitors
of anion exchange did not. Dissociation of the inhibition of anion exchange
and deoxygenation- induced cation flux indicates that the DIDS effect on
deoxygenation- induced cation movements does not involve the
well-characterized stilbene binding site of the anion exchanger. These data
provide evidence for a membrane constituent on the external surface of
oxygenated sickle cells capable of interacting with DIDS to prevent the
increase in cation permeability associated with sickling.
Volume 76,
Issue 1,
pp. 212-220,
07/01/1990
Copyright © 1990 by The American Society of Hematology

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