title: Effect of nitric oxide on histamine-induced cytological transformations in parietal cells in isolated human gastric glands.
abstract: Previous studies have shown that nitric oxide (NO) inhibits histamine-induced gastric acid secretion in isolated human gastric glands. NO synthase has been found to be present in the human oxyntic mucosa and has been suggested to serve as a paracrine regulator of gastric acid secretion. Histamine stimulation of parietal cells induces cytoskeletal rearrangements, recruitment of H+/K+-ATPase-rich tubulovesicles to the apical membrane and expansion of intracellular canaliculi. The aim of the present study was thus to investigate (i) the effect of an NO donor on histamine-induced cytological transformations and (ii) the influence of increased [Ca2+]i on NO-induced morphological changes in human parietal cells. Human gastric glands were isolated and subjected to the NO donor SNAP prior to histamine administration. [Ca2+]i was increased by photolysis of the caged Ca2+ compound NP-EGTA. The distribution of F-actin, ezrin, and H+/K+-ATPase was assessed by confocal microscopy. Ultrastructural analysis was performed using transmission electron microscopy. SNAP did not influence the histamine-induced translocation of F-actin, ezrin, and H+/K+-ATPase but prevented an increase in the canalicular size. Elevation of [Ca2+]i in resting cells was found to mimic histamine-induced intraparietal cell transformations; however, NO-induced parietal cell morphology was unaffected by a rise in [Ca2+]i. These results indicate that NO inhibits secretion of fluid into the canalicular lumen without affecting membrane recruitment and that this effect is Ca2+-insensitive.
authors.affiliation: Department of Biomedicine and Surgery, Division of Cell Biology, Linköping University, S-581 85 Linköping, Sweden. annbe@ibk.liu.se
authors.forename: Anna
authors.initials: A
authors.lastname: Berg
authors.forename: Stefan
authors.initials: S
authors.lastname: Redéen
authors.forename: Sven Erik
authors.initials: SE
authors.lastname: Sjöstrand
authors.forename: Ann-Charlott
authors.initials: AC
authors.lastname: Ericson
mesh_terms: D000199:Actins / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000328:Adult; D002118:Calcium / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology; D018494:Histamine Agents / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D018613:Microscopy, Confocal; D009569:Nitric Oxide / Q000502:physiology*; D010295:Parietal Cells, Gastric / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010782:Photolysis; D000099149:Ezrin
chemical_list: D000199:Actins; D000251:Adenosine Triphosphatases; D002118:Calcium; D003598:Cytoskeletal Proteins; D006632:Histamine; D018494:Histamine Agents; D009569:Nitric Oxide; D000099149:Ezrin