Annals of the New York Academy of
Sciences, 529, (1988)
Characterization of the interrelationship of the
secretory activities of gastric tissue
Casciano, C. and Bennun, A.
The understanding of the process of gastric cytoprotection
requires the elucidation of the mechanism of bicarbonate (HCO3-)
secretion. This includes the identification of the source(s)
of HCO3- and mechanism(s) that regulate the secretion. These
studies have been hindered by the means chosen to prevent
interference of acid secretion on the assay for HCO3-. The
methods previously used for the removal of this acid interference,
which employed isolated stomach preparations, include the
following: the use of histamine antagonists, which incompletely
inhibit basal acid secretion; treatment of the tissue with
nonphysiological doses of SCN-, which combines with H+ in
the mucosal solution to form HSCN, which then diffuses back
to the cell cytosol to dissipate the proton gradient; and
extrapolation from experiments conducted on isolated antral
mucosa, which is devoid of parietal cells and thus free of
acid interference.
Sch 28080 [2-methyl-8-(phenylmethoxy)imidazo[1,2-a]-pyridine-3-acetonitrile],
a potent inhibitor of the H+ / K+ ATPase pump in the parietal
cell, was found to have both antisecretory and cytoprotective
activity. It was also shown to stimulate HCO3- secretion in
the isolated guinea-pig gastric mucosa. These phar¬macologic
properties of MPIPA afford it a potentially valuable role
for furthering studies of HCO3- secretion by the fundic mucosa.
Therefore, it was desirable to characterize the mechanism
through which MPIPA inhibits acid and stimulates HCO3- secretions
in the isolated fundic mucosa of the rat. Accordingly, slices
from this tissue were incubated in HCO3-/CO2 -free bathing
media, and the effect of the drug was examined in relationship
to intracellular and extracellular agonists of acid secretion.