Lanthanides are transported by ionophore A23187 and mimic calcium in the histamine secretion process

Ionophore A23187 induced histamine release from peritoneal rat mast cells in the presence of lanthanum or terbium as it did in the presence of calcium. Low concentrations of lanthanides (10(-5) to 2 X 10(-4) M) were more efficient than similar concentrations of calcium. The effect of low concentrations of calcium and lanthanides were additive. Increasing the concentration of lanthanides above 10(-3) M decreased histamine release. This decrease was partly reversed by calcium. Calmodulin inhibitors, phenothiazines, R24571 and mepacrine, inhibited the histamine release induced by either calcium or lanthanides. Zn2+, a calmodulin inhibitor transported by A23187, inhibited more potently the calcium-dependent histamine release. Lanthanides decrease histamine release induced by 48/80 in the absence of added calcium. These data show that ionophore A23187 can transport lanthanides across the plasma membrane of mast cells, allowing the trivalent cations to substitute for calcium in the activation of calmodulin or calmoduline-like proteins.