AJP - Gastrointestinal and Liver Physiology, Vol 253, Issue 3 359-G368, Copyright © 1987 by American Physiological Society
Conservative and nonconservative inhibitors of gastric acid secretion
E. B. Ekblad and V. Licko
Inhibitors of the initial step (H2-antagonist) and of the final step
(thiocyanate, SCN-; and nitrite, NO2-) were used to study the dynamics of
acid secretion in isolated frog gastric mucosa. Tissues were mounted in
flow-through chambers, and the acid secretion rate (SR) was recorded on a
pH-stat microprocessor. Continuous presence of H2-antagonist decreases the
SR to a lower steady state, and on removal the SR returns to basal SR,
causing a net loss of acid, the nonconservative effect. The amount of lost
acid is a unique function of exposure, thus, independent of the patterns
(pulses or steps) of inhibition. In contrast, continuous presence of SCN-
or NO2- (below 3 mM) results in an undershoot in SR with a return to basal
SR, whereas at higher concentrations there is no return. Removal of these
inhibitors causes an overshoot in SR with return to basal SR. The rebound
acid is equal to acid suppressed by NO2- and low concentration of SCN-,
resulting in no net loss of acid, the conservative effect, whereas at high
concentrations of SCN- there is an apparent loss of acid. In maximally
secreting tissue the overshoot of SR is not observed. However, the acid is
not lost, merely delayed. In resting tissue NO2- also merely delays the
exit of the acid produced in response to forskolin. The rebound acid is
proposed to reside in a sequestered "acid" pool that is stable for at least
120 min. Results with NO2- and SCN- suggest an effect on a saturable exit
enzyme, possibly the K+-H+-ATPase.
