MEDIATION OF IRON UPTAKE AND RELEASE IN ERYTHROID-CELLS BY PHOTODEGRADATION PRODUCTS OF NIFEDIPINE

The effects of five Ca2+ channel antagonists on iron uptake by erythro id cells were investigated using rabbit reticulocytes and erythrocytes , and transferrin-bound iron and non-transferrin-bound iron (Fe(II)). All of the antagonists except nifedipine inhibited iron uptake, but on ly at relatively high concentrations (10-100 mu M). Nifedipine markedl y stimulated the uptake of Fe(II) but nor transferrin-bound iron, but only after it had been photodegraded to its nitrosophenylpyridine deri vative. This compound was found to mediate Fe(II) exchange between the cytosol and extracellular medium in both directions with both reticul ocytes and erythrocytes, but not by the known iron transport processes . The effect could be reversed by washing the cells with ice-cold NaCl solution. It appeared to be relatively specific for Fe(II) since phot odegraded nifedipine had little effect on the uptake of Fe(III) or Mn2 +. it is suggested that the nitrosopyridine derivative of nifedipine c an act as an Fe(II) ionophore and may be of use as an adjuvant in chel ator therapy with desferrioxamine in conditions of iron overload.