Low monoamine oxidase B in peripheral organs in smokers.
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.
Fowler
Joanna S
JS
Chemistry Department and Medical Department, Brookhaven National Laboratory, Upton, NY 11973, USA. fowler@bnl.gov
Logan
Jean
J
Wang
Gene-Jack
GJ
Volkow
Nora D
ND
Telang
Frank
F
Zhu
Wei
W
Franceschi
Dinko
D
Pappas
Naomi
N
Ferrieri
Richard
R
Shea
Colleen
C
Garza
Victor
V
Xu
Youwen
Y
Schlyer
David
D
Gatley
S John
SJ
Ding
Yu-Shin
YS
Alexoff
David
D
Warner
Donald
D
Netusil
Noelwah
N
Carter
Pauline
P
Jayne
Millard
M
King
Payton
P
Vaska
Paul
P
D006801:Humans; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000493:pharmacokinetics; D012642:Selegiline / Q000493:pharmacokinetics; D012907:Smoking / Q000378:metabolism*; D014055:Tomography, Emission-Computed
D008996:Monoamine Oxidase Inhibitors; D012642:Selegiline; D008995:Monoamine Oxidase