Low monoamine oxidase B in peripheral organs in smokers
Low monoamine oxidase B in peripheral organs in smokers
复制标题
DOI：
10.1073/pnas.1833106100
复制
发表时间：
2003-09-30
影响因子：
11.1
通讯作者：
Vaska, P
中科院分区：
文献类型：
--
作者：
Fowler, JS;Logan, J;Vaska, P
终止儿茶酚胺和血管活性膳食胺的作用的主要机制之一是通过单胺氧化酶（MAO）氧化。吸烟者已被证明具有降低的脑单胺氧化酶水平，导致推测烟草烟雾对单胺氧化酶的抑制可能是吸烟的一些行为和流行病学特征的基础。由于吸烟会使外周器官和大脑暴露于单胺氧化酶抑制化合物，我们怀疑吸烟者是否也会降低外周器官中的单胺氧化酶水平。在这里，我们比较了非吸烟者和吸烟者外周器官中的MAO B，采用正电子发射断层扫描和连续扫描的MAO B特异性放射性示踪剂，L-[C-11]丙炔苯丙胺和氘取代的L-[C-11]丙炔苯丙胺（L-[C-11]丙炔苯丙胺-D2）。通过使用氘同位素效应评估结合特异性。我们发现，与非吸烟者相比，吸烟者外周器官中的单胺氧化酶B显著减少，特别是在心脏、肺和肾脏中。下降幅度从33%到46%不等。由于MAO B分解儿茶酚胺和其他生理活性胺，包括尼古丁释放的胺，因此其抑制可能会改变交感神经张力以及中枢神经递质活性，这可能导致吸烟的医学后果。此外，虽然大多数关于烟雾致癌特性的重点都放在肺部和上呼吸道上，但这一发现突出了这样一个事实，即身体的多个器官也暴露于烟草烟雾中大量的化学化合物。
One of the major mechanisms for terminating the actions of catecholamines and vasoactive dietary amines is oxidation by monoamine oxidase (MAO). Smokers have been shown to have reduced levels of brain MAO, leading to speculation that MAO inhibition by tobacco smoke may underlie some of the behavioral and epidemiological features of smoking. Because smoking exposes peripheral organs as well as the brain to MAO-inhibitory compounds, we questioned whether smokers would also have reduced MAO levels in peripheral organs. Here we compared MAO B in peripheral organs in nonsmokers and smokers by using positron emission tomography and serial scans with the MAO B-specific radiotracers,L-[C-11]deprenyl and deuterium-substituted L-[C-11]deprenyl (L-[C-11]deprenyl-D2). Binding specificity was assessed by using the deuterium isotope effect. We found that smokers have significantly reduced MAO B in peripheral organs, particularly in the heart, lungs, and kidneys, when compared with nonsmokers. Reductions ranged from 33% to 46%. Because MAO B breaks down catecholamines and other physiologically active amines, including those released by nicotine, its inhibition may alter sympathetic tone as well as central neurotransmitter activity, which could contribute to the medical consequences of smoking. In addition, although most of the emphases on the carcinogenic properties of smoke have been placed on the lungs and the upper airways, this finding highlights the fact that multiple organs in the body are also exposed to pharmacologically significant quantities of chemical compounds in tobacco smoke.