Mast cell activation involves plasma membrane potential- and thapsigargin-sensitive intracellular calcium pools

被引:13
|
作者
Kassel, O [1 ]
Amrani, Y [1 ]
Landry, Y [1 ]
Bronner, C [1 ]
机构
[1] UNIV STRASBOURG 1,LAB NEUROIMMUNOPHARMACOL,INSERM,U425,F-67401 ILLKIRCH GRAFFENS,FRANCE
关键词
calcium; compound; 48/80; IgE receptors; mast cell; thapsigargin;
D O I
10.1111/j.1472-8206.1995.tb00530.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The regulation and role of the intracellular Ca2+ pools were studied in rat peritoneal mast cells. Cytosolic free calcium concentration ([Ca2+](i)) was monitored in fura-2 loaded mast cells. In the presence of Ca2+ and K+, compound 48/80 induced a biphasic increase in [Ca2+](i) composed of a fast transient phase and an apparent sustained phase. The sustained phase was partially inhibited by the addition of Mn2+. DTPA, a cell-impermeant chelator of Mn2+, reversed this inhibition, suggesting that a quenching of fura-2 fluorescence occurs in the extracellular medium. In the absence of extracellular Ca2+, the transient phase, but not the sustained one, could be preserved, provided that mast cells were depolarized. The transient phase was completely abolished by thapsigargin, a microsomal Ca2+-ATPase inhibitor. Maximum histamine release induced by either compound 48/80 or antigen was obtained in the absence of added Ca2+ only when mast cells were depolarized. These histamine releases were inhibited by low doses (< 30 nM) of thapsigargin. Thapsigargin at higher doses induced histamine release which was unaffected by changing the plasma membrane potential, but was completely dependent on extracellular Ca2+, showing that a Ca2+ influx is required for thapsigargin-induced exocytosis. Together, these results suggest that the mobilization of Ca2+ from thapsigargin sensitive-intracellular pools induced by compound 48/80 or antigen is sufficient to trigger histamine release. The modulation of these pools by the plasma membrane potential suggest their localization is close to the plasma membrane.
引用
收藏
页码:531 / 539
页数:9
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