Tobacco and Public Health - TCSC Indonesia

170
CIGARETTE SCIENCE: ADDICTION BY DESIGN
Tourette’s syndrome, schizophrenia, and depression (Belluardo et al. 2000). For some
of these disorders, the use of nAChRs’ agonists may represent either a preventative or a
symptomatic treatment (Mihailescu and Drucker-Colin 2000).
Nicotine binding to receptors in the brain, augments the release of numerous
neurotransmitters, including dopamine, serotonin, norepinephrine, acetylcholine,
gamma-aminobutyric acid, and glutamate (Quattrocki et al. 2000). The binding of
nicotine to the receptor increases the production of acetylcholine receptors in neurons
and affects neural tissue through this stimulus in the presence of acetylcholine.
The result of chronic receptor-mediated stimulation of these tissues is an alteration
of nearly all components of the neuroendocrine system including the
corticosteroids, adrenal hormones, serotonin, and pituitary hormones (US Surgeon
General 1988).
It is important to note that the nicotine receptor is able to bind a wide range of
compounds as agonists (e.g. acetylcholine, epibatidine, imperialine, pyridine) and
receptor antagonists (e.g. succinylcholine). This raises the possibility that some of the
compounds in the complex mixture of cigarette smoke have nicotinic (or anti-nicotinic)
activity that is not factored into the standard nicotine yield measurements.
While chronic agonist stimulation of most neuroreceptors results in a down-regulation
of receptor numbers in tissues, the nicotine receptor is apparently up-regulated in the
hippocampus and thalamus regions of the brain under such conditions (Kobayashi et al.
1999). The up-regulation of these receptors precedes the development of tolerance to
nicotine (Kobayashi et al. 1999). The degree of nicotine receptor binding correlates
with the number of cigarettes smoked per day (Benhammou et al. 2000). The role of
non-nicotine factors in this up-regulation is not clear, and there have been suggestions
that other compounds in tobacco smoke (e.g. anabasine) influence this regulation
(Yates et al. 1995). It has been shown that ethanol treatment in vitro results in a
reduced level of receptor up-regulation (Gorbounova et al. 1998).
Nicotine receptors on human neurological cells in vitro can serve as biomarkers for
nicotinic activity in cigarette total particulate matter. Such in vitro assay systems have
the potential to help determine the biological nicotinic activity of cigarette smoke.
If ‘denicotinized’ cigarettes were to become marketed, biological measures such as this
would be needed to ensure that the removal of nicotine is accompanied by a removal of
nicotinic activity in the smoke.
Factors that influence the absorption or delivery of nicotine
The standard measured nicotine yield of a cigarette is determined by:
◆ The nicotine content of the tobacco
◆ The static burn rate or amount of tobacco consumed during puffing
◆ The pressure drop of the tobacco column
◆ Porosity of the wrapper and or ventilation at the filter