Schachter E Neil, Zuskin Eugenija, Goswami Satindra, Castranova Vincent, Siegel Paul, Whitmer Mike, Gadgil Aneal
Mount Sinai Hospital, New York, NY 10029, USA.
Chest. 2003 Mar;123(3):862-8. doi: 10.1378/chest.123.3.862.
To determine the effects of tobacco dust extract (TDE) on isolated guinea pig tracheal smooth muscle.
A controlled, in vitro smooth-muscle study of the effect of pharmacologic agents on TDE.
The effect of TDE on isolated guinea pig tracheal smooth muscle was tested using water-soluble extracts of dust obtained from machines in a cigarette manufacturing plant. Dose-related contractions of nonsensitized guinea pig trachea were demonstrated using these extracts. The dust extracts contained significant quantities of bacterial components (eg, endotoxin). Pharmacologic studies were performed by pretreating guinea pig tracheal tissue with drugs known to modulate smooth-muscle contraction: atropine, indomethacin, pyrilamine, nordihydroguaretic acid, acivicin, bromophenacyl bromide, 3,4,5-trimethoxybenzoic acid-8-(diethylamino)octyl ester, captopril, and capsaicin.
Atropine strikingly reduced the contractile effects of these extracts. Inhibition of contraction by blocking other mediators was less complete. There was no inhibition of contraction by hexamethonium (10(-4) mol/L, 10(-5) mol/L, 10(-6) mol/L), suggesting that nicotine was not the major contractile mediator of TDE. A separate analysis using different molecular weight fractions of TDE indicated that the constrictor activity appears to be primarily in the fraction with a molecular weight < 10 kd. Additionally, the constrictor effect resided entirely in the nonlipid fraction of the extract. We suggest that TDE causes dose-related airway smooth-muscle constriction by nonimmunologic mechanisms involving a variety of airway mediators and possibly cholinergic receptors.
The bronchoconstrictor activity of TDE resides primarily in its low molecular weight, nonlipid fraction, and hexamethonium studies suggest that this agent is not nicotine.
确定烟草尘提取物（TDE）对分离的豚鼠气管平滑肌的影响。
一项关于药物制剂对TDE作用的体外平滑肌对照研究。
使用从卷烟厂机器中获取的粉尘水溶性提取物，测试TDE对分离的豚鼠气管平滑肌的作用。使用这些提取物证明了未致敏豚鼠气管的剂量相关收缩。粉尘提取物含有大量细菌成分（如内毒素）。通过用已知可调节平滑肌收缩的药物预处理豚鼠气管组织进行药理学研究：阿托品、消炎痛、吡苄明、去甲二氢愈创木酸、阿西维辛、溴苯甲酰溴、3,4,5-三甲氧基苯甲酸-8-（二乙氨基）辛酯、卡托普利和辣椒素。
阿托品显著降低了这些提取物的收缩作用。通过阻断其他介质对收缩的抑制不太完全。六甲铵（10⁻⁴mol/L、10⁻⁵mol/L、10⁻⁶mol/L）对收缩无抑制作用，表明尼古丁不是TDE的主要收缩介质。对TDE不同分子量组分的单独分析表明，收缩活性似乎主要存在于分子量<10kd的组分中。此外，收缩作用完全存在于提取物的非脂质部分。我们认为，TDE通过涉及多种气道介质和可能的胆碱能受体的非免疫机制引起剂量相关的气道平滑肌收缩。
TDE的支气管收缩活性主要存在于其低分子量、非脂质部分，六甲铵研究表明该物质不是尼古丁。
