title: Demand for Zn2+ in acid-secreting gastric mucosa and its requirement for intracellular Ca2+.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
authors.affiliation: Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: JingJing
authors.initials: J
authors.lastname: Liu
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Kohler
authors.forename: Amy L
authors.initials: AL
authors.lastname: Blass
authors.forename: Juliet A
authors.initials: JA
authors.lastname: Moncaster
authors.forename: Anca
authors.initials: A
authors.lastname: Mocofanescu
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Marcus
authors.forename: Eleanor A
authors.initials: EA
authors.lastname: Blakely
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Bjornstad
authors.forename: Chitra
authors.initials: C
authors.lastname: Amarasiriwardena
authors.forename: Noel
authors.initials: N
authors.lastname: Casey
authors.forename: Lee E
authors.initials: LE
authors.lastname: Goldstein
authors.forename: David I
authors.initials: DI
authors.lastname: Soybel
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D005456:Fluorescent Dyes; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism*; D013058:Mass Spectrometry; D008856:Microscopy, Fluorescence; D011083:Polycyclic Compounds; D011817:Rabbits; D015032:Zinc / Q000378:metabolism*
chemical_list: C451182:FluoZin-3; D005456:Fluorescent Dyes; D011083:Polycyclic Compounds; D015032:Zinc; D002118:Calcium