Bae J, Stuenkel E L, Loch-Caruso R
Department of Environmental and Industrial Health, The University of Michigan, Ann Arbor, Michigan, 48109-2029, USA.
Toxicol Appl Pharmacol. 1999 Mar 15;155(3):261-72. doi: 10.1006/taap.1998.8614.
Polychlorinated biphenyls (PCBs) are persistent environmental pollutants associated with spontaneous abortion and shortened gestation length in women and animals. In previous studies, we showed that PCB mixtures and noncoplanar ortho-substituted PCB congeners increased contractions in pregnant rat uterus. In the present study, we hypothesized that the PCB mixture Aroclor 1242 (A1242) stimulates oscillatory uterine contraction in pregnant uterus by increasing intracellular calcium concentration ([Ca2+]i). Pretreatment of uterine strips with ryanodine or thapsigargin, to deplete specific intracellular calcium stores, did not prevent the increased frequency of oscillatory contraction due to 50 microM A1242, whereas thapsigargin effectively blocked carbachol-induced stimulation of uterine contraction. However, 100 microM A1242 was unable to increase contraction in the absence of extracellular calcium or in the presence of the voltage-operated L-type calcium channel blocker nifedipine. A1242 (100 microM) was observed to partially depolarize the cell membrane of myometrial cells from pregnant rats, as measured with a potential-sensitive carbocyanine dye. Changes of [Ca2+]i were monitored in single myometrial cells loaded with the fluorescent calcium-sensitive probe fura-2. Cells exposed to 100 microM A1242 showed a delayed and sustained increase of [Ca2+]i, and this increase was completely blocked in the absence of extracellular calcium or the presence of nifedipine. Therefore, the data suggest that depolarization of the cell membrane by A1242 enabled myometrial cells to increase [Ca2+]i through activation of voltage-operated calcium channels, and the increased [Ca2+]i consequently stimulated contraction of uterine smooth muscle.
多氯联苯（PCBs）是一种持久性环境污染物，与人类和动物的自然流产及妊娠时长缩短有关。在之前的研究中，我们发现多氯联苯混合物及非共面邻位取代多氯联苯同系物会增强孕鼠子宫的收缩。在本研究中，我们推测多氯联苯混合物Aroclor 1242（A1242）通过增加细胞内钙浓度（[Ca2+]i）来刺激妊娠子宫的振荡性子宫收缩。用ryanodine或毒胡萝卜素预处理子宫条以耗尽特定的细胞内钙储备，不能阻止50微摩尔A1242引起的振荡性收缩频率增加，而毒胡萝卜素能有效阻断卡巴胆碱诱导的子宫收缩刺激。然而，在无细胞外钙或存在电压门控L型钙通道阻滞剂硝苯地平的情况下，100微摩尔A1242无法增强收缩。用电压敏感的羰花青染料测量发现，A1242（100微摩尔）可使孕鼠子宫肌层细胞膜部分去极化。用荧光钙敏感探针fura-2加载的单个子宫肌层细胞中监测[Ca2+]i的变化。暴露于100微摩尔A1242的细胞显示[Ca2+]i延迟且持续增加，在无细胞外钙或存在硝苯地平的情况下，这种增加被完全阻断。因此，数据表明A1242引起的细胞膜去极化使子宫肌层细胞能够通过激活电压门控钙通道增加[Ca2+]i，而增加的[Ca2+]i进而刺激子宫平滑肌收缩。
