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Smoking Damages Key Regulatory Enzyme in the Lung

UPTON, NY
- 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
by scientists at the U.S. Department of Energy's Brookhaven National
Laboratory and their collaborators. 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 lead author Joanna Fowler, director of the Center for Translational Neuroimaging at Brookhaven.

Fowler and collaborators from Brookhaven, the National Institute on Drug Abuse (NIDA), and Stony Brook University 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 nine
smokers and nine 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 regulate blood pressure.

The
scans revealed 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, environmental agents - even nicotine.

Fowler
and her colleagues have been studying MAO for more than 30 years.
Previous research by their group revealed that smokers have reductions
in another subtype of the enzyme, MAO B, in the brain and in a variety
of the body's peripheral organs when compared to nonsmokers (see: this release).

"These
studies showing for the first time that smokers have reduced levels of
MAO in their brains and in certain peripheral organs shed mechanistic
light on some of the more puzzling aspects of smoking, including a
reduced rate of Parkinson's disease in smokers and a high rate of
smoking among people with depression and those addicted to other
substances," Fowler said. The role played by MAO in other conditions
associated with smoking may also be significant and deserves further
investigation, considering the differences observed in the enzyme level
between smokers and nonsmokers, she said.

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. This research was funded by the Office of
Biological and Environmental Research within the U.S. Department of
Energy's Office of Science, and by NIDA, a division of the National
Institutes of Health. PET imaging is a direct outgrowth of the
Department of Energy's long-standing investment in basic physics
research.

"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 - which have
played such an important role in introducing new nuclear medicine
procedures into the practice of health care," Fowler said

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