Effect of Nitric Oxide on Histamine-Induced Cytological Transformations in Parietal Cells in Isolated Human Gastric Glands

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.