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.

The Source of Carbon Dioxide for Gastric Acid Production

“…The increase in carbonic anhydrase activity would have the potential for the hydration of more carbon dioxide and the production of a greater quantity of gastric acid in the parietal cell canaliculi. The dynamic process of parietal cell canalicular changes related to HCl activators and inhibitors are associated with cytoskeletal and cytochemical rearrangements as has been demonstrated by in vitro studies (Agnew et al, 1999; Berg et al, 2007).…”