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

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.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+).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

Validation of an intrinsic groundwater pollution vulnerability methodology using a national nitrate database.

The importance of groundwater for potable supply, and the many sources of anthropogenic contamination, has led to the development of intrinsic groundwater vulnerability mapping. An Analysis of Co-Variance and Analysis of Variance are used to validate the extensively applied UK methodology, based upon nitrate concentrations from 1,108 boreholes throughout England and Wales. These largely confirm the current aquifer and soil leaching potential classifications and demonstrate the benefits of combining soil and low permeability drift information. European legislation such as the Water Framework Directive will require more dynamic assessments of pollutant risk to groundwater. These results demonstrate that a number of improvements are required to future intrinsic groundwater vulnerability methodologies. The vertical succession of geological units must be included, so that non-aquifers can be zoned in the same way as aquifers for water supply purposes, while at the same time recognising their role in influencing the quality of groundwater in deeper aquifers. Classifications within intrinsic vulnerability methodologies should be based upon defined diagnostic properties rather than expert judgement. Finally the incorporation into groundwater vulnerability methodologies of preferential flow in relation to geological deposits, soil type and land management practices represents a significant, but important, future challenge