Smoking damages key regulatory enzyme in the lung

08/30/05

Study in Journal of Nuclear Medicine uses PET, radiotracer to track enzyme in smokers, nonsmokers

RESTON, Va.-- Smoking appears to reduce a key enzyme in the lungs, possibly contributing to some of smoking's deleterious health effects, according to a study published in the September issue of the Journal of Nuclear Medicine. The study, which used a radiotracer to track the enzyme, also shows that smokers had a lower concentration of the tracer in the bloodstream than nonsmokers did, leading to speculation that smokers and nonsmokers may respond differently to a variety of substances administered by inhalation or intravenously, including therapeutic, anesthetic and addictive drugs.

"The effects of smoking on human health are enormous; yet, little is known about the pharmacologic effects of smoking on the human body apart from the effects of nicotine," noted Joanna S. Fowler, Ph.D., program director of the Brookhaven Center for Translational Neuroimaging in Upton, N.Y. Researchers from Brookhaven National Laboratory, the National Institute on Drug Abuse and the State University of New York at Stony Brook used positron emission tomography (PET) scanning and a tracer chemical that binds to a specific form of the enzyme monoamine oxidase (MAO A) to track MAO A levels in both smokers and nonsmokers. With whole-body PET imaging, researchers could measure the concentration and movement of the radiotracer and MAO A, a subtype of the enzyme crucial to mood regulation and one that breaks down chemical compounds that elevate blood pressure, said the Society of Nuclear Medicine member.

In the study, "Comparison of Monoamine Oxidase A in Peripheral Organs in Nonsmokers and Smokers," researchers traced the MAO A subtype in nine smokers and nine nonsmokers, discovering that MAO A was fairly well "intact" in all of the peripheral organs except in smokers' lungs, said Fowler. Smokers had MAO A levels that were 50 percent lower than in nonsmokers, she said, noting that a prior study had also shown a significant reduction of MAO A in smokers' brains.

MAO A breaks down many compounds that affect blood pressure, and the lung is a major metabolic organ in degrading some of these compounds, Fowler said. So reduced levels of MAO A in smokers' lungs may be a significant factor contributing to some of the physiological effects of smoking, including changes in blood pressure and pulmonary function.

Smokers' lungs also held onto the tracer chemical much longer than nonsmokers, and the delivery of tracer into the arterial blood supply was much lower for smokers, particularly for the first few minutes after being injected, Fowler added. This finding could imply that smokers and nonsmokers respond differently to other substances that enter the body via the bloodstream, including therapeutic drugs, anesthetics, abused substances and environmental agents--even nicotine.

Cigarette smoking, "the most damaging of all addictive substances," remains the leading cause of preventable death and has negative health impacts on people at all stages of life, said Fowler, and has been in the headlines recently with the death of ABC "World News Tonight" anchorman Peter Jennings. Cigarette smoking accounts for 440,000 deaths each year in the United States, or nearly one of every five deaths, according to the Centers for Disease Control and Prevention. Smoking kills more Americans than AIDS, illegal drugs, alcohol, car accidents, suicides and murders combined and increases one's chances of developing lung, bladder, esophageal and throat cancers; chronic lung diseases; and coronary heart and cardiovascular diseases.

Fowler and her colleagues have been studying MAO for more than 30 years. The U.S. Department of Energy (DOE) Office of Biological and Environmental Research and the National Institutes of Health have provided funding for this study, said Fowler. She added, "It's important that the public know about the benefits derived from the DOE's long-term investments in basic science--especially in radioisotope and radiotracer chemistry and imaging physics--that have played such an important role in introducing new nuclear medicine procedures into the practice of health care."

"Comparison of Monoamine Oxidase A in Peripheral Organs in Nonsmokers and Smokers" appears in the September issue of the Journal of Nuclear Medicine, which is published by the Society of Nuclear Medicine. Fowler co-authored the article with Jean Logan, Ph.D., Colleen Shea, M.S., Victor Garza, M.S., Youwen Xu, M.S., Yu-Shin Ding, Ph.D., David Alexoff, BSE, and Donald Warner, all with Brookhaven National Laboratory's chemistry department; Gene-Jack Wang, M.D., Frank Telang, M.D., Noelwah Netusil, RN, Pauline Carter, RN, Millard Jayne, RN, Payton King, M.S, and Paul Vaska, Ph.D., all with Brookhaven National Laboratory's Medical Department; Nora D. Volkow, M.D., National Institute on Drug Abuse, Bethesda, Md.; Wei Zhu, Ph.D., Department of Applied Mathematics and Statistics, State University of New York at Stony Brook; and Dinko Franceschi, M.D., Department of Radiology, State University of New York at Stony Brook.

Source: Eurekalert & others

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