Demand for Zn2+ in Acid-Secreting Gastric Mucosa and Its Requirement for Intracellular Ca2+

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.

Neurochemical Characterization of Zinc Transporter 3-Like Immunoreactive (ZnT3+) Neurons in the Intramural Ganglia of the Porcine Duodenum

“…Moreover, extracellular Zn is not the only player in the animal tissues. For example, Ca 2+ facilitates Zn uptake, and oxidative dysregulation of intracellular Zn could be amplified by dysregulation of intracellular Ca 2+ homeostasis (Liu et al 2011 ). This potential relationship between Zn and Ca 2+ levels may in part explain the role of Zn and Zn transporters in the intestinal secretion (Liu et al 2011 ).…”

Zinc Sensing Receptor Signaling, Mediated by GPR39, Reduces Butyrate-Induced Cell Death in HT29 Colonocytes via Upregulation of Clusterin

“…Zinc has been specifically shown to play a role in digestive system function under normal conditions or stress [25], [26], [27]. Furthermore, zinc accelerates healing of gastric ulcers and drugs containing zinc are commonly used to enhance colonocytes cell proliferation and growth, although the mechanism is unknown [25], [28].…”

“…Zinc is an essential micronutrient that has an established role in enhancing epithelial proliferation and survival [19] , [20] , [21] , [22] , moreover, zinc signaling is suggested to play a role in cancer [23] , [24] . Zinc has been specifically shown to play a role in digestive system function under normal conditions or stress [25] , [26] , [27] . Furthermore, zinc accelerates healing of gastric ulcers and drugs containing zinc are commonly used to enhance colonocytes cell proliferation and growth, although the mechanism is unknown [25] , [28] .…”

Human Zinc Deficiency: Discovery to Initial Translation

“…The total serum protein concentration and the percentage albumin were normal, while gamma globulin was increased. There was no baseline free gastric acid after histamine stimulation or after 6 wk of treatment [zinc nutriture affects gastric parietal cell function (12)]. …”