Low monoamine oxidase B in peripheral organs in smokers

被引:59
作者
Fowler, JS [1 ]
Logan, J
Wang, GJ
Volkow, ND
Telang, F
Zhu, W
Franceschi, D
Pappas, N
Ferrieri, R
Shea, C
Garza, V
Xu, YW
Schlyer, D
Gatley, SJ
Ding, YS
Alexoff, D
Warner, D
Netusil, N
Carter, P
Jayne, M
King, P
Vaska, P
机构
[1] Brookhaven Natl Lab, Dept Chem, Upton, NY 11973 USA
[2] Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA
[3] SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11794 USA
关键词
D O I
10.1073/pnas.1833106100
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
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收藏
页码:11600 / 11605
页数:6
相关论文
共 44 条
[1]   PLASMA INPUT FUNCTION DETERMINATION FOR PET USING A COMMERCIAL LABORATORY ROBOT [J].
ALEXOFF, DL ;
SHEA, C ;
FOWLER, JS ;
KING, P ;
GATLEY, SJ ;
SCHLYER, DJ ;
WOLF, AP .
NUCLEAR MEDICINE AND BIOLOGY, 1995, 22 (07) :893-904
[2]   DEUTERIUM ISOTOPE EFFECTS IN RELATION TO CHEMICAL MECHANISM OF MONOAMINE OXIDASE [J].
BELLEAU, B ;
MORAN, J .
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, 1963, 107 (03) :822-&
[3]  
Benedetti MS, 1998, J NEURAL TRANSM-SUPP, P149
[4]  
BENOWITZ NL, 1988, NEW ENGL J MED, V319, P1318
[5]   MONOAMINE-OXIDASE-A AND MONOAMINE-OXIDASE-B ACTIVITIES IN HEAVY SMOKERS [J].
BERLIN, I ;
SAID, S ;
SPREUXVAROQUAUX, O ;
OLIVARES, R ;
LAUNAY, JM ;
PUECH, AJ .
BIOLOGICAL PSYCHIATRY, 1995, 38 (11) :756-761
[6]   Trace amines: Identification of a family of mammalian G protein-coupled receptors [J].
Borowsky, B ;
Adham, N ;
Jones, KA ;
Raddatz, R ;
Artymyshyn, R ;
Ogozalek, KL ;
Durkin, MM ;
Lakhlani, PP ;
Bonini, JA ;
Pathirana, S ;
Boyle, N ;
Pu, XS ;
Kouranova, E ;
Lichtblau, H ;
Ochoa, FY ;
Branchek, TA ;
Gerald, C .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (16) :8966-8971
[7]   CLINICAL AND BIOCHEMICAL ASPECTS OF DEPRESSIVE-DISORDERS .3. TREATMENT AND CONTROVERSIES [J].
CALDECOTTHAZARD, S ;
SCHNEIDER, LS .
SYNAPSE, 1992, 10 (02) :141-168
[8]  
Centers for Disease Control and Prevention (CDC), 2003, MMWR Morb Mortal Wkly Rep, V52, P303
[9]   Parkinson disease: A new link between monoamine oxidase and mitochondrial electron flow [J].
Cohen, G ;
Farooqui, R ;
Kesler, N .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (10) :4890-4894
[10]   Inhibition of monoamine oxidase B in the brains of smokers [J].
Fowler, JS ;
Volkow, ND ;
Wang, GJ ;
Pappas, N ;
Logan, J ;
MacGregor, R ;
Alexoff, D ;
Shea, C ;
Schlyer, D ;
Wolf, AP ;
Warner, D ;
Zezulkova, I ;
Cilento, R .
NATURE, 1996, 379 (6567) :733-736