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SK&F 96365对中性粒细胞样HL-60细胞中细胞外钙离子依赖性超氧阴离子生成的影响。

Effect of SK&F 96365 on extracellular Ca2+ -dependent O2- production in neutrophil-like HL-60 cells.

作者信息

Gallois A, Bueb J L, Tschirhart E

机构信息

Neuroimmunology and Inflammation, Centre de Recherche Public-Santé, Luxembourg, Luxembourg.

出版信息

Eur J Pharmacol. 1998 Nov 20;361(2-3):293-8. doi: 10.1016/s0014-2999(98)00728-6.

DOI:10.1016/s0014-2999(98)00728-6
PMID:9865520
Abstract

Store-operated Ca2+ entry is referred to a capacitative current activated by Ca2+ -stores depletion in various non-excitable cells. Neutrophil-like HL-60 cells responded to N-formyl-L-Methionyl-L-Leucyl-L-Phenylalanine (fMLP) by an early O2- production preceded by a [Ca2+]i rise. Cell stimulation in the absence of extracellular Ca2+ resulted in a major reduction of [Ca2+]i rise and O2- production. A purported inhibitor of store-operated Ca2+ entry, SK&F 96365 (1-(beta-(3-(4-methoxy-phenyl)propoxyl)-4-methoxy-phenetyl)- 1H-imidazole hydrochloride), inhibited extracellular Ca2+ -dependent [Ca2+]i rise by 30% but did not alter O2- production. In conclusion, SK&F 96365 did not modify extracellular Ca2+ -dependent O2- production, despite a significant but limited reduction in fMLP-activated membrane Ca2+ fluxes which can be ascribed to store-operated Ca2+ entry. Furthermore, Ca2+ influx is necessary for a full induction and maintenance of the biological response.

摘要

储存式钙离子内流是指在各种非兴奋性细胞中,由钙离子储存耗竭激活的一种电容性电流。类中性粒细胞HL-60细胞对N-甲酰-L-蛋氨酰-L-亮氨酰-L-苯丙氨酸(fMLP)的反应是,在细胞内钙离子浓度([Ca2+]i)升高之前先有早期超氧阴离子(O2-)生成。在无细胞外钙离子的情况下进行细胞刺激,会导致[Ca2+]i升高和O2-生成大幅减少。一种据称的储存式钙离子内流抑制剂SK&F 96365(1-(β-(3-(4-甲氧基苯基)丙氧基)-4-甲氧基苯乙基)-1H-咪唑盐酸盐)可使细胞外钙离子依赖性的[Ca2+]i升高降低30%,但不改变O2-生成。总之,尽管fMLP激活的膜钙离子通量因储存式钙离子内流而有显著但有限的减少,但SK&F 96365并未改变细胞外钙离子依赖性的O2-生成。此外,钙离子内流对于生物反应的充分诱导和维持是必要的。

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