Yan Ren-Ming, Chiung Yin-Mei, Pan Chien-Yuan, Liu Jenn-Hwa, Liu Pei-Shan
Department of Microbiology, Soochow University, Shihlin, Taipei, Taiwan.
Toxicology. 2008 Nov 20;253(1-3):28-35. doi: 10.1016/j.tox.2008.07.066. Epub 2008 Aug 9.
para-Dichlorobenzene (DCB), a deodorant and an industrial chemical, is a highly volatile compound and is known to be an indoor air contaminant. Because of its widespread use and volatility, the toxicity of DCB presents a concern to industrial workers and public. Some toxic aspects of DCB have already been focused but its effects on neuronal signal transduction have been hitherto unknown. The effects of DCB on the cytosolic calcium homeostasis are investigated in human neuroblastoma SH-SY5Y cells in this study. DCB, above 200 microM, was found to induce a rise in cytosolic calcium concentration that could not be counteracted by nicotinic acetylcholine receptor (nAChR) and muscarinic acetylcholine receptor (mAChR) antagonists but was partially inhibited by thapsigargin. To understand the actions of DCB on the acetylcholine receptors, we investigated its effects on the changes of cytosolic calcium concentration following nicotinic AChR stimulation with epibatidine and muscarinic AChR stimulation with methacholine in human neuroblastoma SH-SY5Y cells. DCB inhibited the cytosolic calcium concentration rise induced by epibatidine and methacholine with respective IC(50)s of 34 and 294 microM. The inhibitions of DCB were not the same as thapsigargin's inhibition. In the electrophysiological observations, DCB blocked the influx currents induced by epibatidine. Our findings suggest that DCB interferes with the functional activities of AChR, including its coupling influx currents and cytosolic calcium elevations.
对二氯苯（DCB）是一种除臭剂和工业化学品，是一种高度挥发性化合物，已知是室内空气污染物。由于其广泛使用和挥发性，DCB的毒性引起了工业工人和公众的关注。DCB的一些毒性方面已经受到关注，但其对神经元信号转导的影响迄今尚不清楚。本研究在人神经母细胞瘤SH-SY5Y细胞中研究了DCB对细胞质钙稳态的影响。发现浓度高于200微摩尔的DCB可诱导细胞质钙浓度升高，这种升高不能被烟碱型乙酰胆碱受体（nAChR）和毒蕈碱型乙酰胆碱受体（mAChR）拮抗剂抵消，但可被毒胡萝卜素部分抑制。为了解DCB对乙酰胆碱受体的作用，我们在人神经母细胞瘤SH-SY5Y细胞中研究了其对用依博加因刺激烟碱型AChR和用醋甲胆碱刺激毒蕈碱型AChR后细胞质钙浓度变化的影响。DCB抑制依博加因和醋甲胆碱诱导的细胞质钙浓度升高，其半数抑制浓度（IC50）分别为34和294微摩尔。DCB的抑制作用与毒胡萝卜素的抑制作用不同。在电生理观察中，DCB阻断了依博加因诱导的内流电流。我们的研究结果表明，DCB干扰AChR的功能活动，包括其偶联的内流电流和细胞质钙升高。
