Schuller H M
Department of Pathobiology, College of Veterinary Medicine, University of Tennessee, Knoxville 37901-1071.
Biochem Pharmacol. 1989 Oct 15;38(20):3439-42. doi: 10.1016/0006-2952(89)90112-3.
The objective of this study was to investigate a potential involvement of nicotinic cholinergic receptors in the mediation of cell type specific biological effects of nicotine and the two tobacco-related nitrosamines N-nitrosodiethylamine (DEN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) on human lung cells. Three well differentiated human lung cancer cell lines that have been reported previously to possess ultrastructural and biochemical features of normal pulmonary neuroendocrine cells, Clara cells and alveolar type II cells, respectively, were used for these experiments. The effects of nicotine, DEN, and NNK on cell proliferation and its modulation by established antagonists of nicotinic and muscarinic cholinergic receptors were studied. In the neuroendocrine cell line, nicotine and the two nitrosamines caused a strong stimulation of cell proliferation that was inhibited by antagonists of nicotinic cholinergic receptors. In the cell lines with features of Clara cells and alveolar type II cells, nicotine did not stimulate cell proliferation. Both nitrosamines stimulated cell proliferation in the cell line with Clara cell features. This effect was not changed by pre-exposure to cholinergic antagonists. The data suggest a selective uptake of nicotine and the two nitrosamines via nicotinic cholinergic receptors in pulmonary neuroendocrine cells.
本研究的目的是调查烟碱型胆碱能受体在介导尼古丁以及两种烟草相关亚硝胺——N-亚硝基二乙胺（DEN）和4-（甲基亚硝胺基）-1-（3-吡啶基）-1-丁酮（NNK）对人肺细胞的细胞类型特异性生物学效应中可能发挥的作用。此前有报道称，三种高度分化的人肺癌细胞系分别具有正常肺神经内分泌细胞、克拉拉细胞和II型肺泡细胞的超微结构和生化特征，本实验使用了这些细胞系。研究了尼古丁、DEN和NNK对细胞增殖的影响以及烟碱型和毒蕈碱型胆碱能受体的既定拮抗剂对其的调节作用。在神经内分泌细胞系中，尼古丁和这两种亚硝胺强烈刺激细胞增殖，而烟碱型胆碱能受体拮抗剂可抑制这种增殖。在具有克拉拉细胞和II型肺泡细胞特征的细胞系中，尼古丁不会刺激细胞增殖。两种亚硝胺均刺激具有克拉拉细胞特征的细胞系中的细胞增殖。预先暴露于胆碱能拮抗剂并不会改变这种效应。数据表明，肺神经内分泌细胞可通过烟碱型胆碱能受体选择性摄取尼古丁和这两种亚硝胺。
