Absolute Dependence on Chloride for Acid Secretion in Isolated Gastric Glands

Isolated glands from the rabbit gastric mucosa lost their ability to accumulate H+ ions when incubated in Cl–-free solutions, as measured by accumulation of the weak base aminopyrine (AP). Simultaneously, basal oxygen consumption was significantly increased (+56%). Addition of histamine or dibutyryl cyclic AMP (db-cAMP) further increased the respiration but only a minor increment in the AP accumulation was seen. Addition of Cl– dose-dependently increased the AP accumulation back to normal basal values, a function which was coupled with a progressive decrease in oxygen consumption down to the normal level. ed50 for AP accumulation was 15.0 mM Cl–. SCN– also decreased the respiratory rate but did not restore AP accumulation. Increasing the K+ concentration of the Cl–-free solution 10-fold did not per se affect the AP ratio, but facilitated the rise in AP accumulation upon addition of CI–. At standard CI– concentrations the final AP ratio was significantly increased above that of glands incubated at normal K+ concentrations. Addition of Br– to the chloride-free medium induced responses which were indistinguishable from those of CI–, whereas I– showed less affinity and was inhibitory at higher concentrations (above 20 mM). Studies on AP accumulation kinetics showed that addition of CI– to glands pretreated with db-cAMP did not induce a more rapid accumulation than that seen in glands to which db-cAMP and CI– were added simultaneously. This might indicate that db-cAMP does not induce a morphological transformation of the parietal cell into a secreting state in the absence of Cl–. As one explanation for the results obtained, a Cl–-HCO3– exchange mechanism in the secretory membrane is proposed which implies that HCO3– handling in the secretory membrane is impaired in the absence of CI– and that this could lead to a neutralization of the H+ ions formed.