Low monoamine oxidase B in peripheral organs in smokers

Abstract

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.

Fig. 1.

Structures of l-[¹¹C]deprenyl and deuterium-substituted l-[¹¹C]deprenyl (l-[¹¹C]deprenyl-D2). The C–H (C–D) bond in the methylene carbon of the propargyl group is the bond that is cleaved in the rate contributing step of MAO-catalyzed oxidation.

Fig. 2.

Whole-body images of carbon-11 distribution in one of the nonsmokers and one of the smokers. These subjects were scanned with l-[¹¹C]deprenyl, and scanning was started at 25-min post-radiotracer injection. Red is the highest radiotracer concentration on the color scale, and images are scaled so that they can be compared directly.

Fig. 3.

Model terms for nonsmokers and smokers. (a) Comparison of MAO B for different organs as assessed by the model term, λk₃, in nonsmokers and smokers, which was determined from time-activity data from PET scans, and the arterial plasma radiotracer concentration after injection of l-[¹¹C]deprenyl-D2. (b) Comparison of the plasma to tissue transfer constant, K₁, in different organs for the same group of nonsmokers and smokers.