Fowler Joanna S, Logan Jean, Wang Gene-Jack, Volkow Nora D, Telang Frank, Zhu Wei, Franceschi Dinko, Pappas Naomi, Ferrieri Richard, Shea Colleen, Garza Victor, Xu Youwen, Schlyer David, Gatley S John, Ding Yu-Shin, Alexoff David, Warner Donald, Netusil Noelwah, Carter Pauline, Jayne Millard, King Payton, Vaska Paul
Chemistry Department and Medical Department, Brookhaven National Laboratory, Upton, NY 11973, USA.
Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11600-5. doi: 10.1073/pnas.1833106100. Epub 2003 Sep 12.
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-[11C]deprenyl and deuterium-substituted l-[11C]deprenyl (l-[11C]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.
儿茶酚胺和血管活性膳食胺作用终止的主要机制之一是通过单胺氧化酶(MAO)进行氧化。研究表明,吸烟者脑内MAO水平降低,这引发了一种推测,即烟草烟雾对MAO的抑制作用可能是吸烟某些行为和流行病学特征的潜在原因。由于吸烟会使外周器官以及大脑接触到MAO抑制性化合物,我们不禁要问,吸烟者外周器官中的MAO水平是否也会降低。在这里,我们通过正电子发射断层扫描以及使用MAO B特异性放射性示踪剂l-[11C]司来吉兰和氘取代的l-[11C]司来吉兰(l-[11C]司来吉兰-D2)进行系列扫描,比较了非吸烟者和吸烟者外周器官中的MAO B。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MAO B显著降低,尤其是在心脏、肺和肾脏中。降低幅度在33%至46%之间。由于MAO B会分解儿茶酚胺和其他生理活性胺,包括尼古丁释放的胺,其抑制作用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,尽管对烟雾致癌特性的大多数关注都集中在肺部和上呼吸道,但这一发现凸显了一个事实,即体内多个器官也会接触到烟草烟雾中具有药理学意义的大量化合物。