Correlation between leukotriene D4-induced contraction and cytosolic calcium elevation: a quantitative and simultaneous evaluation in smooth muscle.

Correlation between leukotriene D4-induced contraction and cytosolic calcium elevation: a quantitative and simultaneous evaluation in smooth muscle.
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白三烯 D4 诱导的收缩与胞浆钙升高之间的相关性:平滑肌的定量和同步评估。

DOI:
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发表时间:
1994
影响因子:
3.5
通讯作者:
S. Nicosia
S. Nicosia
中科院分区:
医学2区
文献类型:
--
作者:
D. Oliva;M. Accomazzo;S. Giovanazzi;S. Nicosia

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短句来源本研究通过测量豚鼠回肠纵肌条带载钙荧光指示剂Fura 2的力发展和胞内钙离子浓度升高,探讨了钙离子作为细胞内信使在白三烯(LT) d4诱导的肌肉收缩中的作用。加入LTD4后,观察到张力和胞质钙浓度[ca++]i同时增加。LTD4的累积应用诱导了肌肉张力和[Ca++]i的浓度依赖性增加,在大约6至9 nM处达到半最大效应。两个参数之间存在统计学上显著的正相关(r = 0.993, P < 0.001)。在洗浴液中去除钙,同时加入7.5 mM EGTA,完全阻止了钙水平或力发展的任何增加,从而表明钙++流入的作用,而不是细胞内储存的释放。所有测试的LTD4拮抗剂都能够抵消白三烯对[Ca++]i和张力增加的影响。然而,尽管LY171883以平行方式将LTD4曲线向右移动,但FPL 55712和ICI 198,615在逆转LTD4对[Ca++]i和张力的影响方面表现为非竞争性拮抗剂。因此,这些结果强烈提示LTD4引起的肌肉张力变化可归因于豚鼠回肠胞浆游离Ca++浓度的变化。
The role of Ca++ as an intracellular messenger in leukotriene (LT)D4-induced muscle contraction was investigated by measuring force development and elevation in cytosolic Ca++ concentration simultaneously in strips of guinea pig ileal longitudinal muscle loaded with the fluorescent calcium indicator Fura 2. Upon addition of LTD4, a simultaneous increase in tension and cytosolic calcium concentration, [Ca++]i, was observed. Cumulative applications of LTD4 induced concentration-dependent increases in both muscle tension and [Ca++]i, being the half-maximal effect reached at approximately 6 to 9 nM. A statistically significant positive correlation (r = 0.993, P < .001) exists between the two parameters examined. Removal of calcium in the bathing solution, accompanied by addition of 7.5 mM EGTA, completely prevented any increase in either calcium levels or force development, thus indicating a role for Ca++ influx, rather than a release from intracellular stores. All of the LTD4 antagonists tested were able to counteract the effect of the leukotriene on both [Ca++]i and tension increase. However, although LY171883 shifted both of the LTD4 curves to the right in a parallel fashion, FPL 55712 and ICI 198,615 behaved as non-competitive antagonists in reversing the effect of LTD4 on [Ca++]i and tension. Thus, these results strongly suggest that changes in muscle tension induced by LTD4 are attributable to changes in cytosolic free Ca++ concentrations in guinea pig ileum.