Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

III. Gastric Secretions
417
FIGURE 14-1 Movement of ions across the
mucosal (apical) and serosal (basal) cell membranes
of the parietal during HCl secretion.
Glu·Gly·Pro·Trp·Met·Glu·Glu·Glu·Glu·Glu·Ala·Tyr·Gly·Trp·Met·Asp·Phe·NH 2
FIGURE 14-2 Amino acid sequence of porcine gastrin I ( Gregory, 1966 ). Gastrin II differs from gastrin I by the
presence of a sulfate ester group on the single tyrosyl residue.
Trp-Met-Asp-Phe-NH 2 , is identical in all species so far
studied ( Gregory, 1967 ). The tetrapeptide has all of the
activities of the natural hormone. It is not as potent as the
parent molecule, but lengthening of the peptide chain can
increase activity.
Gastrin-releasing peptide—as well as luminal peptides,
digested protein, and acetylcholine—stimulates gastrin
secretion from G cells and affects histamine release from
enterochromaffin-like cells ( Simpson, 2005 ). Gastrin is
the only hormone known to simulate HCl ( Walsh and
Grossman, 1975 ).
3 . Histamine
Histamine secreted locally within the mucosa has a major
effect on the function of oxyntic cells ( Soll and Grossman,
1978 ). For many years, histamine has been recognized as a
potent stimulant of HCl production, but this effect was not
inhibited by traditional antihistaminic drugs (H 1 antagonists),
and until the demonstration by Black et al. (1972)
of H 2 receptors in the stomach (the atrium and uterus), the
physiological role of histamine in HCl secretion was controversial.
Specific H 2 antagonists (cimetidine) now have
been shown to inhibit the secretory response not only to
histamine but to other secretory stimuli as well ( Grossman
and Konturek, 1974 ).
The complex of oxyntic cell receptors involved in the
control of oxyntic cell function is shown in Figure 14-3 .
When the H 2 receptor of the oxyntic cell is occupied by
histamine, basal lateral adenylate cyclase is activated,
resulting in increased cellular cyclic AMP (cAMP) and in
a sustained secretory response. The secretogogue action of
cAMP is mediated by the activity of cAMP-dependent protein
kinases ( Chew, 1985 ).
Cholinergic stimulation of the oxyntic cell involves
type I muscarinic receptors and a calcium activation pathway.
Calmodulin inhibitors such as trifluoroperazine inhibit
H secretion ( Raphael et al., 1984 ). The Ca-calmodulin
system may influence the rate of cAMP synthesis, and a
more distal site of action has been suggested by the identification
of a Ca-dependent protein kinase activity in a membrane
fraction prepared from oxyntic cells that was rich in
H , K -ATPase (Schlatz et al., 1981). A specific receptor
for gastrin has been demonstrated on oxyntic cells and a
specific gastrin antagonist, proglutamide, inhibits H production.
Gastrin appears to act synergistically with histamine
and acetylcholine (AcCh) to regulate H production
but the actual mechanism of action of gastrin is unknown.