Abstract

Background and AimsRecent work has suggested that Zn2+ plays a critical role in regulating acidity within the secretory compartments of isolated gastric glands. Here, we investigate the content, distribution and demand for Zn2+ in gastric mucosa under baseline conditions and its regulation during secretory stimulation.Methods and FindingsContent and distribution of zinc were evaluated in sections of whole gastric mucosa using X-ray fluorescence microscopy. Significant stores of Zn2+ 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, 70Zn2+, 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 70Zn2+ 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 Zn2+ was monitored using the fluorescent zinc reporter, fluozin-3, by measuring increases in free intracellular concentrations of Zn2+ {[Zn2+]i} during exposure to standard extracellular concentrations of Zn2+ (10 µM) for standard intervals of time. Under resting conditions, demand for extracellular Zn2+ increased with exposure to secretagogues (forskolin, carbachol/histamine) and under conditions associated with increased intracellular Ca2+ {[Ca2+]i}. Uptake of Zn2+ was abolished following removal of extracellular Ca2+ or depletion of intracellular Ca2+ stores, suggesting that demand for extracellular Zn2+ increases and depends on influx of extracellular Ca2+.ConclusionsThis study is the first to characterize the content and distribution of Zn2+ in an organ of the gastrointestinal tract. Our findings offer the novel interpretation, that Ca2+ integrates basolateral demand for Zn2+ with stimulation of secretion of HCl into the lumen of the gastric gland. Similar connections may be detectable in other secretory cells and tissues.

Highlights

  • For many years, investigation of Zn2+ transport in the gastrointestinal tract has focused on nutritional requirements that maintain body stores and pathologic consequences of inadequate intake [1,2,3]

  • Our findings offer the novel interpretation, that Ca2+ integrates basolateral demand for Zn2+ with stimulation of secretion of HCl into the lumen of the gastric gland

  • Homogeneous signals for Fe are observed throughout the glandular mucosa, deep to the surface epithelium, in areas known to be populated by mitochondria-rich parietal cells [31,32]

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Summary

Introduction

Investigation of Zn2+ transport in the gastrointestinal tract has focused on nutritional requirements that maintain body stores and pathologic consequences of inadequate intake [1,2,3]. Recent reports have begun to explore the mechanisms that regulate cellular homeostasis of Zn2+ in mucosal cells of the gastrointestinal tract [15,16,17,18,19] and its potential influence on mucosal integrity and function [20,21]. Of the content and distribution of Zn2+ within the mucosa, or of the mechanisms that regulate the flow of Zn2+ into the parietal cell during secretory stimulation. Recent work has suggested that Zn2+ plays a critical role in regulating acidity within the secretory compartments of isolated gastric glands. We investigate the content, distribution and demand for Zn2+ in gastric mucosa under baseline conditions and its regulation during secretory stimulation

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