The Contribution of cocoa additive to cigarette smoking addiction

Page 54 of 207 RIVM report 650270002
Serotonin
chewing of nicotine gum (4-8 mg nicotine) resulted in a transient increase in platelet
5-HT by about 100% in non-smokers, but not in smokers. In conclusion, smoking of
cigarettes can cause an increase in platelet serotonin, most likely via enhanced supply
of serotonin from enterochromaffin cells, which can be stimulated via nicotine
receptors (10).
Metabolism
Serotonin found in enterochromaffin cells and neurons is synthesized in situ from
tryptophan. Tryptophan is first hydroxylated to 5-hyroxytryptophan by enzym
tryptophan-5-hydroxylase and is then decarboxylated to serotonin by non-specific
aromatic L-amino acid decarboxylase. Serotonin is then taken up into secretory
granules and stored.
Most of the serotonin, endogenous or ingested, undergoes oxidative deamination by
monoamine oxidase to form 5-hydroxyindoleacetaldehyde. This is promptly
degraded, mainly by further oxidation, to 5-hydroxyindoleacetic acid (5-HIAA) by
aldehyde dehydrogenase; 5-hydroxyindoleacetalhyde is also reduced (by alcohol
dehydrogenase) to 5-hydroxytryptophol (5-HTOL). The three enzymes are present in
liver and various tissues that contain serotonin, including the brain and the lung (6).
Serum serotonin is inactivated by pulmonary and vascular endothelial monoamine
oxidase, hepatic inactivation and cellular reuptake. Rapid inactivation of unbound
serotonin appears to be an important part of normal serotonergic activity (13, 34).
Excretion
The principal metabolite, 5-HIAA, is excreted in the urine, along with much smaller
amounts of 5-HTOL, mainly as the glucuronide or sulfate. About 2 to 10 mg of 5-
HIAA is excreted daily by normal adults as a result of metabolism of endogenous
serotonin. Patients with malignant carcinoid (tumor of neuroendocrine cells) excrete
larger amounts. Ingestion of ethyl alcohol diverts 5-hydroxyindoleacetaldehyde from
the oxidative route to the reductive pathway, because of the elevated concentration of
NADH. This greatly increases excretion of 5-HTOL and correspondingly reduces that
of 5-HIAA (6). Ingestion of serotonin rich food (banana or walnuts) elevated the
excretion of 5-HIAA in the urine. Smoking of 20- 30 cigarettes per day had no
influence on the 5-HIAA urinary excretion (3).
The pulmonary microvascular endothelium has been shown to be a very important
component in the clearance of many circulating bioactive compounds through the
pulomonary tissue. It was discovered that serotonin is extensively removed (by about
70%) during a single passage through the lungs of dogs as well as in humans (13).
Kinetic parameters
An amount of serotonin roughly equal to that present in the body is synthesized each
day. Turnover times of serotonin in brain and gastrointestinal tract have been
estimated at about 1 and 17 hours, respectively (6).