AJP - Gastrointestinal and Liver Physiology, Vol 240, Issue 3 232-G238, Copyright © 1981 by American Physiological Society
Mechanism of action of SCN in isolated gastric glands
S. J. Hersey, C. S. Chew, L. Campbell and E. Hopkins
Isolated gastric glands were used to study the mechanism of acid secretory
inhibition by thiocyanate (SCN). It was found that SCN does not act as a
competitive antagonist of histamine nor does SCN prevent the increase in
cellular cAMP associated with histamine stimulation. SCN modifies but does
not prevent the expansion of parietal cell canaliculi, indicating that this
characteristic morphological transition does not require the actual
formation of hydrochloric acid. Low doses (less than 5 mM) of SCN were
found to inhibit aminopyrine accumulation, an index of acid formation, but
do not inhibit either resting or stimulated respiration. Higher doses
(greater than 10 mM) of SCN produce significant inhibition of stimulated
but not resting respiration. These results indicate that SCN has two
actions, i.e., inhibition of acid formation that requires low doses and
inhibition of oxidative metabolism that requires higher doses. Incubation
of glands in high-K+ (108 mM) medium leads to formation of an acid gradient
in the absence of other secretagogues. The gradient was found to be
transient, and its formation does not require oxidative metabolism,
indicating that continued proton pumping is not required. Low doses of SCN
were found to be more effective in dissipating the high-K+-induced gradient
than a similar gradient induced by histamine stimulation. These results
support the hypothesis that SCN inhibits acid secretion by increasing the
rate of proton-gradient dissipation rather than interfering with a
proton-pump mechanism.
