Demand for \(Zn^{2+}\) in Acid-Secreting Gastric Mucosa and Its Requirement for Intracellular \(Ca^{2+}\)

Abstract

Background and Aims:

Recent work has suggested that \(Zn^{2+}\) plays a critical role in regulating acidity within the secretory compartments of isolated gastric glands. Here, we investigate the content, distribution and demand for \(Zn^{2+}\) in gastric mucosa under baseline conditions and its regulation during secretory stimulation. Methods and Findings:

Content and distribution of zinc were evaluated in sections of whole gastric mucosa using X-ray fluorescence microscopy. Significant stores of \(Zn^{2+}\) were identified in neural elements of the muscularis, glandular areas enriched in parietal cells, and apical regions of the surface epithelium. In in vivo studies, extraction of the low abundance isotope, \(^{70}Zn^{2+}\), from the circulation was demonstrated in samples of mucosal tissue 24 hours or 72 hours after infusion (250 µg/kg). In in vitro studies, uptake of \(^{70}Zn^{2+}\) from media was demonstrated in isolated rabbit gastric glands following exposure to concentrations as low as 10 nM. In additional studies, demand of individual gastric parietal cells for \(Zn^{2+}\) was monitored using the fluorescent zinc reporter, fluozin-3, by measuring increases in free intracellular concentrations of \(Zn^{2+}\) \(\{[Zn^{2+}]_i\}\) during exposure to standard extracellular concentrations of \(Zn^{2+}\) (10 µM) for standard intervals of time. Under resting conditions, demand for extracellular \(Zn^{2+}\) increased with exposure to secretagogues (forskolin, carbachol/histamine) and under conditions associated with increased intracellular \(Ca^{2+}\) \(\{[Ca^{2+}]_i\}\). Uptake of \(Zn^{2+}\) was abolished following removal of extracellular \(Ca^{2+}\) or depletion of intracellular \(Ca^{2+}\) stores, suggesting that demand for extracellular \(Zn^{2+}\) increases and depends on influx of extracellular \(Ca^{2+}\). Conclusions:

This study is the first to characterize the content and distribution of \(Zn^{2+}\) in an organ of the gastrointestinal tract. Our findings offer the novel interpretation, that \(Ca^{2+}\) integrates basolateral demand for \(Zn^{2+}\) with stimulation of secretion of HCl into the lumen of the gastric gland. Similar connections may be detectable in other secretory cells and tissues.