Extracellular Mg2+ inhibits both histamine-stimulated Ca(2+)-signaling and exocytosis in human tracheal secretory gland cells.

The effects of extracellular Mg2+ concentration have been investigated on the histamine-stimulated exocytotic process of human tracheal secretory gland (HTG) cells. The exocytosis of secretory granules (SG) was observed concomitantly with dynamic changes of intracellular Ca2+ ([Ca2+]i) and Mg2+ concentrations ([Mg2+]i). The rate of SG exocytosis was appraised by the decrease of quinacrine fluorescence emission. Dynamic changes of [Mg2+]i and [Ca2+]i in HTG cells were determined by the combined use of UV-microspectrofluorometry with Mag-Indo-1 and Indo-1 probes, respectively. High Mg2+ medium significantly inhibited the histamine-stimulated secretion. The influence of the extracellular and intracellular Mg2+ concentrations on [Ca2+]i was analyzed. Basal [Mg2+]i increased from 0.8 mM in a Mg(2+)-free medium to 1.7 mM in 10 mM Mg2+ medium. Histamine induced a [Mg2+]i increase which is dependent on extracellular Mg2+ concentration. The histamine stimulated [Ca2+]i rise was reduced in the presence of elevated Mg2+ extracellular medium and inhibitory effects of extracellular Mg2+ were concomitant with changes in [Mg2+]i. Our data suggest that the inhibition by extracellular Mg2+ of stimulated exocytosis is dependent on both the increase of [Mg2+]i and the inhibition of cytosolic Ca2+ influx.