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providing NO as a neurotransmitter (Forstermann, Closs et al. 1994). However it has also
been found in the spinal cord @un, Dun et al. 1992), in sympathetic ganglia and adrenal
glands @un, Dun et al. 1993; Sheng, Gagne et al. 1993), in the epithelial cells of the lung,
uterus and stomach (Schmidt, Gagne et al.1992), in pancreatic islet cells (Schmidt, Warner et
al. 1992) and in human skeletal muscle (Forstennann, Closs et al. 1994). While in the main
nNOS NO production functions mostly in neurotransmission, it is also utilised to maintain
muscle tone, for example, in the gastrointestinal tract and skeletal muscle. These enzymes are
involved in homeostasis throughout the body from memory, behaviour, circadian rhythms, to
the gastroenterology tract, renal function and reproductive activity. It is likely that this
isoenzyme form is the largest proportion of constitutive NOS in humans (Forstermann, Closs
et al. 1994; Knowles and Moncada 1994). The eNOS isoenzyme within arteries give a basal
level of NO production continuously, which maintains the vascular blood flow and blood
pressure. This isoenzyme is largely responsible for the NO which inhibits platelet aggregation
and platelet adhesion.
3.4.2 Inducible nitric oxide svnthase
The main method of activation, the amount of NO produced and the regulation of this form of
the enzyme is very different from the constitutive forms. The iNOS isoform is regulated at
transcriptional level with activation requiring both a primary and a secondary signal before
the mRNA for the enzyme is produced. The priming agent is interferon gamma (IFNI) or an
interferon inducing agent like bacterial lipopolysaccharide (LPS) (Weinberg, Chapman et al.
1978; Stuehr and Marletta 1985; Drapier, Wietzerbin et al. 1988; Sherman, loro et al. 1991;
Munoz-Fernandez, Fernandez et al. 1992). The category of factors which can act as the
secondary agent continues to be enlarged by every new study. These include interleukin 1
(n-l), IL2, TNFo, tumor necorsis factor p (TNFp), muramyl dipeptide, lipoteichoic acid,
picolinic acid (metabolite of l-tryptophan), ozone, cAMP elevating agents, ultravoilet light,
ozone and trauma (Ding, Nathan et al. 1988; Drapier and Hibbs 1988; Lorsbach, Murphy et
al. 1993; Bastian and Hibbs 1994; Nathan and Xie 1994).In addition, a number of viral and
antimicrobial products from mycobacteium tuberculosis, salmonella typhimuium and
protozoan parasites have also been found to stimulate this form of the enzyme (MacMicking,
North et ^1. 1997; Shoda, Kegerreis et al. 2001; Thoma-Uszynski, Stenger et al. 2001). Some
food components are also capable of inducing NO and may be the mechanism of action of
some food carcinogens, og soybean trypsin inhibitor, beta amylase (Nathan 1997). For
example, nitrites and nitrates are important antimicrobial, flavouring and colouring agents in
meat and fish products (Chow and Hong 2W2).
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