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GASTRIC ACID SECRETION,
BLOOD FLOW, AND MUCOSAL BARRIER FUNCTION
Urethane-anesthetized rats
Acid output is monitored at
set time intervals (2-10 min) through an acutely implanted catheter
by continuous intragastric perfusion and back-titration or by
collection of gastric contents. This model has the advantage
of providing a consistently low basal secretory rate and reliable
assessment of responses to exogenous stimulants of gastric acid
secretion given either peripherally (intravenously, intra-arterially,
intraperitoneally) or centrally (intracerebroventricularly, intracisternally
or microinjection into the brain parenchyma), and to endogenous
stimulants, such as an intragastric meal. In addition, inhibitors
of stimulated gastric acid secretion can be assessed. Examples
of uses for this model include bioassay of newly characterized
peptides or molecular forms of peptides; determinations of the
mechanism or pathway of action of endogenous peptides, such as
in intestinal feedback inhibition of gastric acid secretion;
and studies where the determination of locus of action is important,
such as central versus peripheral site of action. In addition,
measurements of gastric acid secretion can be combined with monitoring
of other gastrointestinal parameters (gastric mucosal blood flow,
gastric motor function, or pancreatic exocrine secretion).
Urethane-anesthetized mice
This is essentially the same
model as described above but modified for mice. Acid output is
monitored at set time intervals (2-10 min) through an acutely
implanted catheter by continuous intragastric perfusion and back-titration.
The anesthetized mouse model enables the study of gastric secretory
physiology which previously has only been studied in an ex vivo
preparation. In contrast to vascularly and luminally perfused
stomach preparations, this in vivo model, recently developed
by the Core, maintains intact all hormonal and intrinsic and
extrinsic neural connections to the stomach while using mice
in which genes for peptides and receptors important in the regulation
of gastric function have been altered.
Awake rats
Gastric acid secretion is measured
by gravity drainage or by continuous intragastric perfusion and
back titration via a chronic gastric cannula in awake rats accustomed
to light restraint in Bollman cages. This model has the obvious
advantage of measuring function in awake animals and of being
cost effective in that these rats can be used repeatedly over
several months. In addition, chronic intravenous and intestinal
cannulas can be implanted in these animals for the assessment
of exogenously administered substances.
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