Mediation of iron uptake and release in erythroid cells by photodegradation products of nifedipine

Calcium-channel blockers do not affect iron transport mediated by divalent metal-ion transporter-1

“…Therefore, nifedipine does not increase metal-ion transport in 3 heterologous expression systems with multiple DMT1 isoforms. Instead, our data support earlier proposals [7][8][9] that PDN is an iron-specific ionophore. The ionophore effect of PDN was independent of DMT1 because (1) it was less apparent when cells overexpressed DMT1 than when DMT1 levels were lower or minimal; and (2) PDN stimulated the uptake of Fe, but not of Mn, while both are DMT1 substrates.…”

“…Nifedipine had no effect on metal-ion transport in cells expressing these isoforms. Other investigators observed that photodegraded nifedipine (PDN) stimulated iron uptake into erythrocytes 7,8 or epidermal keratinocytes. 9 We found that PDN stimulated uptake of Fe 2ϩ , but not Mn 2ϩ , in cells with minimal DMT1 expression (TetR, EV, or uninduced cells), but not in cells in which DMT1 expression was induced.…”

Human iron transporters

“…These results offer nifedipine as a means of modulating iron overload in a fashion that would be off-label use of a USA FDA-approved drug. We [33] have not been able to reproduce the stimulation of DMT1 by nifedipine and suggest that the ability of photodegraded nifedipine to serve as an iron channel [19,44,45] may account for some of their observations. Unfortunately, their statistical analysis [31] supporting the argument that the DMT1 mutation diminishes the loss of serum iron is flawed and the postulated role of DMT1 in supporting exit of iron would make DMT1 join Fpn as an iron exporter.…”

Epidermal desquamation

“…There is considerable information about the expression and regulation of the transferrin receptor, making manipulation of receptor function one potential pathway to increase iron transport into keratinocytes. Pharmacologically, there are several chemical relatives of nifedipine [58,59] that act as iron ionophores and increase iron transport into keratinocytes [60].…”