Dl. Savigni et Eh. Morgan, MEDIATION OF IRON UPTAKE AND RELEASE IN ERYTHROID-CELLS BY PHOTODEGRADATION PRODUCTS OF NIFEDIPINE, Biochemical pharmacology, 51(12), 1996, pp. 1701-1709
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.