Satake Kazuo, Lee Jong-Dae, Shimizu Hiromasa, Uzui Hiroyasu, Mitsuke Yasuhiko, Yue Hong, Ueda Takanori
First Department of Internal Medicine, Fukui University, 23 Shimoaizuki, Matsuokacho, Fukui 910-1193, Japan.
Magnes Res. 2004 Mar;17(1):20-7.
This study investigated the effects of extracellular magnesium concentration ([Mg2+]e; 0.3-3 mM) on intracellular free calcium concentration ([Ca2+]i) and prostacyclin (PGI2) production in cultured human umbilical vein endothelial cells (HUVEC) and vascular smooth muscle cells from rats (VSMC) under basal and agonist-stimulated conditions. We used histamine as agonist which increases [Ca2+]i and PGI2 production in HUVEC, norepinephrine in VSMC. [Mg2+]e dose-dependently increased basal and agonist-stimulated PGI2 production in both cells. [Mg2+]e dose-dependently reduced basal [Ca2+]i in VSMC, but did not influence in HUVEC. In both cells, increasing [Mg2+]e reduced agonist-stimulated [Ca2+]i responses. Furthermore, [Mg2+]e dose-dependently reduced agonist-stimulated [Ca2+]i in Ca(2+)-free buffer, indicating intracellular Ca2+ release. In VSMC, 10(-6) M diltiazem and 10(-7) M nifedipine, Ca2+ channel blockers, reduced agonist-stimulated [Ca2+]i as well as 3 mM Mg2+, but did not affect PGI2 production. [Mg2+]e amplified dose-dependently arachidonic acid-induced PGI2 production in both cells, suggesting the activation of cyclooxygenase and/or PGI2 synthetase. Our results suggest that [Mg2+]e influences intracellular Ca2+ mobilization of not only vascular smooth muscle cells but also endothelial cells by inhibiting both Ca2+ influx and intracellular Ca2+ release. [Mg2+]e enhances PGI2 production in both types of cells, although the mechanism is likely to be independent from Ca2+ mobilization.
本研究调查了细胞外镁离子浓度（[Mg2+]e；0.3 - 3 mM）在基础条件和激动剂刺激条件下对培养的人脐静脉内皮细胞（HUVEC）以及大鼠血管平滑肌细胞（VSMC）内游离钙浓度（[Ca2+]i）和前列环素（PGI2）生成的影响。我们使用组胺作为激动剂来增加HUVEC中的[Ca2+]i和PGI2生成，使用去甲肾上腺素作为VSMC中的激动剂。[Mg2+]e剂量依赖性地增加了两种细胞中基础状态和激动剂刺激下的PGI2生成。[Mg2+]e剂量依赖性地降低了VSMC中的基础[Ca2+]i，但对HUVEC没有影响。在两种细胞中，增加[Mg2+]e均可降低激动剂刺激的[Ca2+]i反应。此外，在无钙缓冲液中，[Mg2+]e剂量依赖性地降低了激动剂刺激的[Ca2+]i，表明细胞内Ca2+释放。在VSMC中，Ca2+通道阻滞剂10(-6) M地尔硫䓬和10(-7) M硝苯地平与3 mM Mg2+一样，可降低激动剂刺激的[Ca2+]i，但不影响PGI2生成。[Mg2+]e剂量依赖性地增强了两种细胞中花生四烯酸诱导的PGI2生成，提示环氧化酶和/或PGI2合成酶被激活。我们的结果表明，[Mg2+]e通过抑制Ca2+内流和细胞内Ca2+释放，不仅影响血管平滑肌细胞的细胞内Ca2+动员，还影响内皮细胞的细胞内Ca2+动员。[Mg2+]e增强了两种类型细胞中的PGI2生成，尽管其机制可能与Ca2+动员无关。
