Effect of Iron Chelators on Dopamine D2 Receptors

Abstract

Nutritional iron deficiency induced in rats causes a selective reduction of [³H]spiperone binding in caudate nucleus. This effect can be reversed by iron supplementation in vivo. The possibility that iron may be involved in the dopamine D₂ receptor was investigated by examining the effect of various iron and noniron chelators on the binding of [³H]spiperone in rat caudate nucleus. Iron chelators 1, 10-phenanthroline, 2,4,6-tripyridyl-s-triazine, α,α′-dipyridyl, and desferrioxamine mesylate inhibited the binding of [³H]spiperone. The inhibition by 1,10-phenanthroline was noncompetitive and reversible. In the presence of FeCl₂ or FeCl₃, the inhibitory effect of 1,10-phenanthroline was potentiated. Iron salts or chelators were without effect on the binding of [³H]dihydroalprenolol to β-adrenoreceptors in caudate nucleus; thus the action of iron chelators on the dopamine D₂ receptor tends to be selective. Incubation of caudate nucleus membrane prepared from iron-deficient rats with FeCl₂ or FeCl₃ did not reverse the diminished binding of [³H]spiperone. The present study indicates that if iron is involved in the physiological regulation of dopamine D₂ agonist-antagonist binding sites, it is more complex than hitherto considered.