EXTRACELLULAR MG2-STIMULATED CA2+-SIGNALING AND EXOCYTOSIS IN HUMAN TRACHEAL SECRETORY GLAND-CELLS( INHIBITS BOTH HISTAMINE)

The effects of extracellular Mg2+ concentration have been investigated on the histamine-stimulated exocytotic process of human tracheal secr etory gland (HTG) cells. The exocytosis of secretory granules (SG) was observed concomitantly with dynamic changes of intracellular Ca2+ ([C a2+](i)) and Mg2+ concentrations ([Mg2+](i)). The rate of SG exocytosi s was appraised by the decrease of quinacrine fluorescence emission. D ynamic 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 extracellula r and intracellular Mg2+ concentrations on [Ca2+](i) was analyzed. Bas al [Mg2+](i) increased from 0.8 mM in a Mg2+-free medium to 1.7 mM in 10 mM Mg2+ medium. Histamine induced a [Mg2+](i) increase which is dep endent on extracellular Mg2+ concentration. The histamine stimulated [ Ca2+](i) rise was reduced in the presence of elevated Mg2+ extracellul ar medium and inhibitory effects of extracellular Mg2+ were concomitan t with changes in [Mg2+](i). Our data suggest that the inhibition by e xtracellular Mg2+ of stimulated exocytosis is dependent on both the in crease of [Mg2+](i) and the inhibition of cytosolic Ca2+ influx. (C) 1 998 Academic Press.