Ionic regulation of human basophil releasability. III. Effects of Na+ and Ca2+ on histamine release induced by different stimuli

The effects of Na⁺ and Ca²⁺ ions on histamine release from human basophils stimulated by anti-IgE, N-formyl-methionyl-leucyl-phenylalanine (FMLP), 4β-phorbol 120myristate 13-acetate (PMA) and Ca²⁺ 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+ 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 Ca²⁺ 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.