Tedeschi A, Palella M, Arquati M, Milazzo N, Miadonna A
Department of Internal Medicine, University of Milan, Ospedale Maggiore Policlinico, Italy.
Pharmacol Res. 1994 Oct-Nov;30(3):229-41. doi: 10.1016/1043-6618(94)80105-3.
The effects of Na+ and Ca2+ ions on histamine release from human basophils stimulated by anti-IgE, N-formyl-methionyl-leucyl-phenylalanine (FMLP), 4 beta-phorbol 12-myristate 13-acetate (PMA) and Ca2+ ionophore A23187 were evaluated. Isosmotic replacement of Na+ in the extracellular medium with the nonpermeant 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 microM: 37.9 +/- 2.3% vs 49.5 +/- 4.3%, n = 8, P < 0.01) and PMA-(160 nM: 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 microM: 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 Ca2+ 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 anti-IgE, FMLP and PMA, whereas it enhances Ca2+ 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.
评估了Na⁺和Ca²⁺离子对由抗IgE、N-甲酰甲硫氨酰-亮氨酰-苯丙氨酸（FMLP）、4β-佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）和Ca²⁺离子载体A23187刺激的人嗜碱性粒细胞组胺释放的影响。用非渗透性Na⁺类似物胆碱⁺或葡萄糖在细胞外培养基中等渗替代Na⁺导致抗IgE-（1/5000：高Na⁺时为43.7±7.3%，低Na⁺时为68.9±7.3%，平均值±标准误，n = 8，P < 0.001）、FMLP-（1μM：37.9±2.3%对49.5±4.3%，n = 8，P < 0.01）和PMA-（160 nM：12.7±0.9%对27.3±4.3%，n = 8，P < 0.05）诱导的组胺释放显著增加，而A23187诱导的组胺释放减少（1μM：90.4±2.4%对45.4±3.4%，n = 8，P < 0.0001）。细胞外Na⁺浓度的逐渐增加伴随着嗜碱性粒细胞对抗IgE、FMLP和PMA反应的降低；相反，A23187诱导的组胺释放被Na⁺上调。在10⁻⁸ - 10⁻⁴ M浓度范围内的Na⁺/H⁺交换体莫能菌素对抗IgE-、FMLP-和PMA诱导的组胺释放具有剂量依赖性抑制作用，但对A23187诱导的组胺释放没有作用。细胞外Ca²⁺上调了上述所有刺激诱导的组胺释放。去除细胞外Na⁺降低了抗IgE、FMLP和PMA诱导的组胺释放对细胞外Ca²⁺的需求。与先前观察到的Na⁺支持大鼠腹膜肥大细胞和大鼠嗜碱性白血病细胞组胺释放的结果相反，这些结果表明Na⁺强烈抑制抗IgE、FMLP和PMA刺激的人嗜碱性粒细胞组胺释放，而增强Ca²⁺离子载体A23187诱导的组胺释放。Na⁺的作用可能与膜电位和/或细胞内pH的调节有关，其作用因细胞类型和用于细胞激活的刺激而异。
