Wisdom D M, Salido G M, Baldwin L M, Singh J
Department of Applied Biology, University of Central Lancashire, England, UK.
Mol Cell Biochem. 1996 Jan 26;154(2):123-32. doi: 10.1007/BF00226780.
This study investigates the effect of magnesium (Mg2+) on the secretory responses and the mobilization of calcium (Ca2+) and Mg2+ evoked by cholecystokinin-octapeptide (CCK-8) in the exocrine rat pancreas. In the isolated intact perfused pancreas CCK-8 (10(-10) M) produced marked increases in juice flow and total protein output in zero and normal (1.1 mM) extracellular Mg2+ [Mg2+]o compared to a much reduced secretory response in elevated (5 mM and 10 mM) [Mg2+]o. Similar effects of perturbation of [Mg2+]o on amylase secretion and 45 Ca2+ uptake (influx) were obtained in isolated pancreatic segments. In pancreatic acinar cells loaded with the fluorescent bioprobe fura-2 acetomethylester (AM), CCK-8 evoked marked increases in cytosolic free Ca2+ concentration [Ca2+]i in zero and normal [Mg2+]o compared to a much reduced response in elevated [Mg2+]o. Pretreatment of acinar cells with either dibutyryl cyclic AMP (DB2 cAMP) or forskolin had no effect on the CCK-8 induced changes in [Ca2+]i. In magfura-2-loaded acinar cells CCK-8 (10(-8) M) stimulated an initial transient rise in intracellular free Mg2+ concentration [Mg2+]i followed by a more prolonged and sustained decrease. This response was abolished when sodium (Na+) was replaced with N-methyl-D-glucamine (NMDG). Incubation of acinar cells with 10 mM Mg2+ resulted in an elevation in [Mg2+]i. Upon stimulation with CCK-8, [Mg2+]i decreased only slightly compared with the response obtained in normal [Mg2+]o. CCK-8 caused a net efflux of Mg2+ in pancreatic segments; this effect was abolished when extracellular sodium [Na+]o was replaced with either NMDG or choline. The results indicate that Mg2+ can regulate CCK-8-evoked secretory responses in the exocrine pancreas possibly via Ca2+ mobilization. Moreover, the movement of Mg2+ in pancreatic acinar cells is dependent upon extracellular Na+.
本研究调查了镁离子（Mg2+）对大鼠胰腺外分泌腺中胆囊收缩素八肽（CCK - 8）诱发的分泌反应以及钙离子（Ca2+）和镁离子动员的影响。在离体完整灌注胰腺中，与细胞外镁离子浓度升高（5 mM和10 mM）时分泌反应大幅降低相比，CCK - 8（10(-10) M）在细胞外镁离子浓度为零和正常（1.1 mM）时显著增加了胰液分泌量和总蛋白输出量。在离体胰腺片段中也获得了细胞外镁离子浓度变化对淀粉酶分泌和45Ca2+摄取（内流）的类似影响。在加载荧光生物探针fura - 2乙酰甲酯（AM）的胰腺腺泡细胞中，与细胞外镁离子浓度升高时反应大幅降低相比，CCK - 8在细胞外镁离子浓度为零和正常时显著增加了胞质游离钙离子浓度[Ca2+]i。用二丁酰环磷腺苷（DB2 cAMP）或福斯可林预处理腺泡细胞对CCK - 8诱导的[Ca2+]i变化没有影响。在加载magfura - 2的腺泡细胞中，CCK - 8（10(-8) M）刺激细胞内游离镁离子浓度[Mg2+]i先出现短暂的初始升高，随后是更持久的下降。当用N - 甲基 - D - 葡糖胺（NMDG）替代钠离子（Na+）时，该反应消失。用10 mM镁离子孵育腺泡细胞导致[Mg2+]i升高。在用CCK - 8刺激时，与在正常细胞外镁离子浓度下获得的反应相比，[Mg2+]i仅略有下降。CCK - 8导致胰腺片段中镁离子净外流；当用NMDG或胆碱替代细胞外钠离子[Na+]o时，该效应消失。结果表明，镁离子可能通过钙离子动员来调节胰腺外分泌腺中CCK - 8诱发的分泌反应。此外，胰腺腺泡细胞中镁离子的移动依赖于细胞外钠离子。
