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The present studies were designed to examine the effect of changes in membrane potential by means of protonophore carbonyl cyanide m-chlorophenylhydrazone (СССР) and variations in the pH of the medium on the secretory response of parietal cells. Studies were performed in vitro using isolated cells from rat stomachs and acid production was indirectly determined by ¹⁴C-aminopyrine (AP) accumulation. СССР affected both basal and histamine-stimulated AP accumulation in a concentration-dependent manner. The AP accumulation ratios depended on pH of the incubation medium; the ratio was lowest at pH 6.6, and increased progressively as the pH of the medium increased to 7.8. Moreover, the decreases in AP accumulation ratios caused by simultanous addition of СССР and AP to cell suspensions compared to those in which СССР was added to incubated cells after achieving the steady-state of AP accumulation were quantitatively similar. These findings suggest that the decrease in AP accumulation due to СССР treaiment is a consequence of an activation of acid secretion rather than an inhibitor of acid production. From the present and previously published data, we propose a working hypothesis: membrane recycling is dependent on changes in apical membrane potential.
The effects of extracellular K⁺ in relation to extracellular Ca²⁺ on acid production were studied. Studies were performed in vitro using isolated cells from rat stomachs, and acid production was indirectly determined by ¹⁴C-aminopyrine (AP) accumulation. In the absence of K⁺ in the incubation medium histamine-stimulated AP accumulation ratios were significantly decreased independently in the presence or absence of extracellular Ca²⁺. Under basal conditions, in the absence of extracellular Ca²⁺ , increasing concentrations of extracellular K⁺ enhanced AP accumulation ratios to significantly higher than those found in the presence of Ca²⁺. In histamine-, cAMP-, and carbachol-stimulated parietal cells, high K⁺ concentrations increased AP accumulation significantly less in Ca²⁺-free than in Ca²⁺-containing media. High K⁺ also induced significantly both an increase in cytosolic free Ca²⁺ concentration and ⁴⁵ Ca²⁺ uptake. The present results confirmed the importance of K⁺ in gastric acid production and suggested a role for Ca²⁺ as a modulator of mechanisms of parietal cell stimulation.
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