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

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Chapter | 14 Gastrointestinal Function
TABLE 14-3 Inhibitors of Oxyntic Cell Function
A. Inhibitors of H , K -ATPase: omeprazole, verapamil,
vanadate
B. Inhibitors of carbonic anhydrase: acetazolamide
C. Inhibitors of cell activation or response
1. Calcium channel antagonists: verapamil, lanthanum
2. Prostaglandin E 2
D. Receptor antagonists
1. H 2 -receptor antagonists: cimetidine, ranitidine
2. Gastrin antagonists: proglumide, benzotript
3. Anticholinergic agents: atropine
E. Inhibitors of calmodulin: trifluoroperazine
FIGURE 14-3 Pathways of secretagogue action on the parietal cell.
Stimulation by gastrin and acetylcholine is mediated by entry of Ca 2
onto the cell. Histamine activates adenylate cyclase with production of
cAMP, the action of which is mediated by protein kinase.
4 . Prostaglandins
Prostaglandins, in addition to inhibiting HCl secretion,
also act on a mucosal cell population that is distinct from
oxyntic cells, which secrete cytoprotective substances
(mucin, glycosaminoglycans). The ulcerogenic effects of
inhibitors of prostaglandin synthesis (indomethacin, aspirin)
apparently are the result of inhibition of the protective
effect of endogenous prostaglandins.
Knowledge of the molecular aspects of receptor function
of HCl secretion by oxyntic cells now provides the
opportunity for specific pharmacological intervention
for the control and treatment of ulcerative diseases of the
upper gastrointestinal tract that appear to be the result of
HCl-induced mucosal injury ( Aclund et al., 1983 ; Becht
and Byars, 1986 ; Campbell-Thompson and Merritt, 1987 ).
Potential therapeutic target sites are listed in Table 14-3 .
Famotidine is commonly administered to dogs and cats.
Injectable ranitidine is administered to foals and horses
during critical stages of gastrointestinal ulceration before
switching to oral administration of omeprazole.
IV . BILIARY SECRETIONS
A . Composition of Bile
The hepatocytes continuously secrete bile into the bile
canaliculi; it is transported through a system of ducts to the
gallbladder, where it is modified, concentrated, and stored.
During digestion, bile is discharged into the lumen of the
duodenum, where it aids in emulsification, hydrolysis, and
solubilization of dietary lipids. The digestive functions of bile
are accomplished almost exclusively by the detergent action
of its major components, the bile salts and phospholipids.
B . Properties of Bile
The carboxyl group of the bile acids is completely ionized
at the pH of bile and is neutralized by Na resulting
in the formation of bile salts. These bile salts are effective
detergents. They are amphipathic molecules that have both
hydrophobic and hydrophilic regions. In low concentrations,
bile salts form molecular or ideal solutions, but when
their concentration increases above a certain critical level,
they form polymolecular aggregates known as micelles.
The concentration at which these molecules aggregate is
called the critical micellar concentration (CMC).
Bile salt micelles are spherical and consist of a central
nonpolar core and an external polar region. Fatty acids,
monoglycerides, and other lipids are solubilized when
they enter the central core of the micelle and are covered
by the outside polar coat. Solubilization occurs only when
the CMC is reached. For the bile salt-monoglyceride-fatty
acid-water system present during normal fat digestion, the
CMC is approximately 2 mM, which normally is exceeded
both in bile and in the contents of the upper small intestine
( Hofmann, 1963, 1967 ). Phospholipids, principally
lecithin, are also major components of bile. In the lumen of