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2.1.2 Exocrine Secretion
PST Stimulates Gastric Secretion
Despite of some in vitro studies in isolated parietal rabbit cells, where PST has been
shown to inhibit gastrin secretion (Lewis et al. 1988 ), in vivo it clearly enhances
gastric activity. This is the case of conscious dogs stimulated with peptone food,
phenylalanine or glucose (Hashimoto et al. 1990 ). Moreover, ECL cells of the gas-
tric antrum have been shown to display high anti PST immunoreactivity, suggesting
its important role in the paracrine regulation of gastric acid secretion through PST
(Hakanson et al. 1995 ).
The mechanism behind gastric stimulation has a clear relationship with the inhi-
bition of parietal cells stimulation by histamine. Such inhibition is interrupted in the
presence of the pertussis toxin, suggesting the existence of a cAMP-dependent
mechanism (Lindstrom et al. 1997 ; Lewis et al. 1988 ).
PST Inhibits the Exocrine Pancreas Secretion
Most studies affirms that PST has a negative effect on exocrine pancreatic secretion,
which has been seen in physiological assays with food stimulation, vagal nerve
arousal, and with CCK-8 treatment (Miyasaka et al. 1989 ). Only very few studies
have been able to show an increased amylase secretion under PST treatment (Arden
et al. 1994 ).
Inhibition of pancreatic secretion was reached by human synthetic PST and by
bovine, porcine, and rat PST, or using only the carboxy-terminal fragment. These
effects appear to be mediated by the presynaptic modulation of acetylcholine release
from the vagal system. Therefore, PST could be a new islet-acinar axis mediator
(Herzig et al. 1992 ).
2.2 PST Exhibits Negative Effects on Cell Proliferation
In HTC rat hepatoma cells, PST presents inhibitory effects on both cell growth and
proliferation, decreasing protein and DNA synthesis. In this case, the underlying
mechanism is the PST mediated nitric oxide (NO) and cyclic GMP (cGMP) produc-
tion. On the other hand, PST can also activate mitogen activated protein kinase
(MAPK), which is a growth signal. In this way, PST is able to increase NO levels in
a dose depend manner, which overtake the MAPK pathway effect. However, if NO
production is blocked by using pharmacological NOS inhibitors, PST action
changes into a growth promoting effect. Therefore, PST effect on cell growth is
depending on the NO availability (Sanchez-Margalet et al. 2001 ).
N.E. Evtikhova et al.