Ionic regulation of human basophil releasability. III. Effects of Na + and Ca 2+ on histamine release induced by different stimuli

Abstract

The effects of Na + and Ca 2+ ions on histamine release from human basophils stimulated by anti-IgE, N-formyl-methionyl-leucyl-phenylalanine (FMLP), 4β-phorbol 120myristate 13-acetate (PMA) and Ca 2+ ionophore A23187 were evaluated. Isosmotic replacement of Na + in the extracellular medium with the non-permeant Na + analogue choline + or with glucose led to a significant increase in anti-IgE- (1/5000: 43.7±7.3% in high Na + vs 68.9±7.3% in low Na + mean± sem, n=8, P<0.001), FMLP- (1 μ m: 37.9 ± 2.3 % vs 49.5 ± 4.3%, n=8 P<0.01) and PMA-(160 n M: 12.7±0.9% vs 27.3±4.3%, n=8, P<0.05) induced histamine release, whereas A23187-induced histamine release was reduced (1 um: 90.4±2.4% vs 45.4±3.4%, n=8, P<0.0001). The progressive increase in extracellular Na + concentration was accompanied by a decrease of basophil response to anti-IgE, FMLP and PMA; in contrast, A23187-induced histamine release was up-regulated by Na + The Na +/H + exchanger monensin, in the concentration range of 10 −8−10 −4 M, exerted a dose-dependent inhibitory effect on anti-IgE-, FMLP- and PMA-induced histamine release, but not on A23187-induced histamine release. Extracellular Ca 2+ up-regulated the histamine release induced by all the above stimuli. Removal of extracellular Na + lowered the requirement of extracellular Ca 2+ for anti-IgE, FMLP- and PMA-induced histamine release. In contrast with previous observations showing that Na + supports histamine release from rat peritoneal mast cells and rat basophilic leukaemia cells, these results indicate that Na + strongly inhibits histamine release from human basophils stimulated by antiIgE, FMLP and PMA, whereas it enhances Ca 2+ ionophore A23187-induced histamine release. The effects of Na + which are probably related to modulation of membrane potential and/or intracellular pH, vary depending on the cell type and the stimulus employed for cell activation.