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.
Sebille
S
S
Laboratoire de Spectroscopie Biomoléculaire, IFR 53, UFR de Pharmacie, Reims, France.
Pereira
M
M
Millot
J M
JM
Jacquot
J
J
Delabroise
A M
AM
Arnaud
M
M
Manfait
M
M
D002118:Calcium / Q000378:metabolism*; D015550:Cell Degranulation / Q000187:drug effects; D002478:Cells, Cultured; D005088:Exocrine Glands / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D005089:Exocytosis / Q000187:drug effects*; D005110:Extracellular Space / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D008274:Magnesium / Q000378:metabolism / Q000494:pharmacology*; D009093:Mucus / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014132:Trachea / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*
D006632:Histamine; D008274:Magnesium; D002118:Calcium