Hsu Shu-Shong, Chen Wei-Chung, Jiann Bang-Ping, Chen Jin-Shyr, Huang Jong-Khing, Chang Hong-Tai, Cheng He-Hsiung, Lo Yuk-Keung, Ho Chin-Man, Jan Chung-Ren
Department of Surgery, Kaohsiung Veterans General Hospital, 813 Kaohsiung, Taiwan.
Arch Toxicol. 2004 Aug;78(8):453-9. doi: 10.1007/s00204-004-0564-1. Epub 2004 Apr 1.
In Madin-Darby canine kidney (MDCK) cells, the effect of maprotiline, an antidepressant, on intracellular Ca(2+) concentration (Ca(2+)) was measured using fura-2. Maprotiline (> 2.5 microM) caused a rapid rise of Ca(2+) in a concentration-dependent manner (EC(50) 200 microM). Maprotiline-induced Ca(2+) rise was reduced by removal of extracellular Ca(2+) or by addition of La(3+), but was not altered by voltage-gated Ca(2+)-channel blockers. Maprotiline-induced Mn(2+) influx-associated fura-2 fluorescence quench directly suggests that maprotiline caused Ca(2+) influx. In Ca(2+)-free medium, thapsigargin, an inhibitor of the endoplasmic reticulum Ca(2+)-ATPase, caused a monophasic Ca(2+) rise, after which the increasing effect of maprotiline on Ca(2+) was nearly abolished; also, pretreatment with maprotiline reduced a portion of thapsigargin-induced Ca(2+) rise. U73122, an inhibitor of phospholipase C, abolished Ca(2+) rise induced by ATP (but not by maprotiline). Overnight incubation with 1-10 microM maprotiline enhanced cell viability, but 20-50 microM maprotiline decreased it. These findings suggest that maprotiline rapidly increases Ca(2+) in renal tubular cells by stimulating both extracellular Ca(2+) influx and intracellular Ca(2+) release, and may modulate cell proliferation in a concentration-dependent manner.
在犬肾上皮细胞（MDCK）中，使用fura - 2测量了抗抑郁药马普替林对细胞内Ca(2+)浓度（[Ca(2+)]i）的影响。马普替林（>2.5 microM）以浓度依赖的方式引起[Ca(2+)]i迅速升高（半数有效浓度EC(50)为200 microM）。去除细胞外Ca(2+)或添加La(3+)可降低马普替林诱导的[Ca(2+)]i升高，但电压门控Ca(2+)通道阻滞剂对其无影响。马普替林诱导的与Mn(2+)内流相关的fura - 2荧光猝灭直接表明马普替林引起了Ca(2+)内流。在无Ca(2+)培养基中，内质网Ca(2+) - ATP酶抑制剂毒胡萝卜素引起[Ca(2+)]i单相升高，之后马普替林对[Ca(2+)]i的增强作用几乎消失；此外，用马普替林预处理可降低部分毒胡萝卜素诱导的[Ca(2+)]i升高。磷脂酶C抑制剂U73122消除了ATP诱导的[Ca(2+)]i升高（但不影响马普替林诱导的升高）。用1 - 10 microM马普替林过夜孵育可增强细胞活力，但20 - 50 microM马普替林则降低细胞活力。这些发现表明，马普替林通过刺激细胞外Ca(2+)内流和细胞内Ca(2+)释放，迅速增加肾小管细胞中的[Ca(2+)]i，并可能以浓度依赖的方式调节细胞增殖。
