Comparison of Monoamine Oxidase A in Peripheral Organs in Nonsmokers and Smokers

Smokers have reduced levels of brain monoamine oxidase A (MAO A) leading to speculation that MAO A inhibition by tobacco smoke may underlie some of the neurophysiologic effects of smoking. Because smoking exposes peripheral organs as well as the brain to MAO A-inhibitory compounds, we determined whether smokers would also have reduced MAO A in peripheral organs. We measured MAO A in peripheral organs in a group of 9 smokers and compared it with a group of nonsmokers studied previously. MAO A was measured using PET and serial scans with the MAO A-specific radiotracers (11)C-clorgyline and deuterium-substituted (11)C-clorgyline ((11)C-clorgyline-D2) using the deuterium isotope effect to assess binding specificity. The time course of radiotracer in the arterial plasma was also measured and data from the tissue time-activity curves and the arterial input function were analyzed using a 3-compartment model to estimate k(3), which represents the rate-limiting step for the irreversible binding of labeled clorgyline to MAO A. Tracer uptake at plateau was reduced with deuterium substitution for the heart, lungs, and kidneys, indicating specificity for MAO. There was no difference in organ uptake at plateau between nonsmokers and smokers though, for the smokers, the efflux of tracer from peak uptake to plateau was slower for the lungs. The area under the time-activity curve for the arterial plasma was also significantly reduced for smokers versus nonsmokers and the reduction occurred in the first few minutes after radiotracer injection. Smokers had an approximately 50% reduction in k(3) when compared with nonsmokers; however, k(3) did not differ for nonsmokers and smokers for the heart and the kidneys. Because MAO A breaks down serotonin, norepinephrine, dopamine, and tyramine, and because the lung is a major metabolic organ in degrading some of these substances, reduced lung MAO A may contribute to some of the physiologic effects of smoking. This study also revealed that the concentration of the radiotracers in the arterial plasma is significantly lower for the smoker versus the nonsmoker and that this appears to be caused in part by retention of the radiotracer in lungs. If this is generally true for other substances that are administered intravenously, then this needs to be considered as a variable that may contribute to different short-term behavioral responses to intravenously administered drugs for nonsmokers versus smokers.