Redox interactions of epinephrine with iron at physiological pH

Abstract

Epinephrine ((R)-4-(1-hydroxy-2-(methylamino)ethyl)-benzene-1,2-diol (Epi) is catecholamine that is released by the sympathetic nervous system and adrenal medulla. It is a physiologically important molecule that acts as a hormone, neurotransmitter, and medication with a broad range of effects 1-3 . Coordinate and redox interaction of Epi with iron affects the interactions with other molecules and its biological effects 4 . In this study, we reported details of redox interactions of Epi with Fe 2+ at pH 7.4, which correspond to the pH value of human plasma Epi and Fe 2+ form a complex that acts as a strong reducing agent. Cyclic voltammetry showed that the positions of E pa and E pc potentials were at approximately -480 and -1100 mV. This implies that Epi and Fe 2+ build a complex with unique redox properties. E1/2 was significantly lower compared to E0' for O 2 /O 2•- (-350 mV). It is important to point out this because superoxide radical anion is produced via spontaneous Fe 2+ reaction with O 2. In other words, Epi-Fe 2+ complex should be capable of reducing transition metals in (patho)physiologicaly relevant complexes that are not susceptible to reduction by O 2. Our results confirmed that Epi-Fe 2+ is capable of reducing the S-S group of glutathione disulfide. On the other hand, Epi acted in a catalyst-like fashion to promote Fe 2+ oxidation by molecular oxygen, and to a facilitated formation of the Epi–Fe 3+ complexes, at physiological pH. In addition, we examined the effects of epinepfrine and Epi/Fe3+ system on glioma cells. Epinephrine alone evokes changes in the membrane currents of glioma cells, but such effects were not observed for the complex with Fe 3+ . This implies that Epi-Fe 3+ might modulate neural activity of Epi in CNS.