Differential inhibitory mechanism of Fe2+ and Fe3+ on contraction of ileal longitudinal smooth muscle.

The mechanism of the inhibition of K(+)-induced contraction caused by ferrous (Fe(2+)) and ferric (Fe(3+)) ions were analysed in guinea-pig ileal longitudinal muscle and taenia coli. Fe(2+)increased the threshold for Ca(2+)-induced contraction in Ca(2+)-free, K(+)-depolarized taenia coli. However, Fe(3+)reduced the size of the maximal response to Ca(2+)without shifting the dose-response curves in taenia coli. Both 10 mM Fe(2+)and 2 mM Fe(3+)caused significant decreases in Ca uptake, as determined by the La method, during K(+)-induced ileal contraction. After treatment with 10 mM Fe(2+)in a state of cell membrane depolarization with K(+)for 30 min, the ileal K(+)-induced tonic contraction was completely restored by washing with medium containing EDTA, a chelator of divalent cations, and Fe(2+)remaining in muscle was almost eliminated by washing. In contrast, after treatment with 2 mM Fe(3+)in K(+)medium, K(+)-induced contraction was reversed only to a slight degree by washing with medium containing deferoxamine, a chelator of trivalent cations, and Fe(3+)in muscle largely remained despite the washing. These results suggest that Fe(2+)binds to the ileal surface membrane and reduces the contraction in response to K(+)mainly by inhibiting Ca(2+)influx. Fe(3+)may exert an inhibitory action on intracellular sites, in addition to the interference of Ca(2+)influx at the cell membrane. Copyright 2001 Academic Press.