Effect of lanthanide ions on histamine secretion from rat peritoneal mast cells

1 Ions of the lanthanide series (lanthanum-lutetium) inhibit histamine release induced by allergen and anti-IgE in the presence of extracellular calcium. The inhibition is dose-dependent in the range 10(-6) to 10(-9) M and there is no marked difference in potency between the lanthanides. 2 The response to lanthanum is biphasic and higher concentrations (10(-4) M) potentiate the release. Maximal concentrations (10(-3) M) again abolish secretion. 3 The effect of concanavalin A is weakly antagonized by lanthanum but strongly inhibited by higher lanthanides. 4 Inhibition of histamine release evoked by basic agents is markedly dependent on the ionic radius of the lanthanide. In the presence of extracellular calcium, dysprosium is the most effective inhibitor. Similar results are observed with dextran. In the absence of calcium, there is a regular increase in inhibition with decreasing ionic radius. 5 Inhibition of release in the presence of calcium is immediate and does not require preincubation with the lanthanide. The antagonism due to lanthanum is competitive and the pA2 values vary with the secretagogue. In contrast, the inhibitory effect in the absence of extracellular calcium increase progressively with time. 6 These results are discussed in terms of the calcium-pools important in histamine release and the mode of action of different secretagogues.