Nitric oxide inhibits gastric acid secretion by increasing intraparietal cell levels of cGMP in isolated human gastric glands

2005 ◽  
Vol 289 (6) ◽  
pp. G1061-G1066 ◽  
Author(s):  
Anna Berg ◽  
Stefan Redéen ◽  
Magnus Grenegård ◽  
Ann-Charlott Ericson ◽  
Sven Erik Sjöstrand
Keyword(s):  
Nitric Oxide ◽  
Gastric Mucosa ◽  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Enzymatic Digestion ◽  
Human Gastric Mucosa ◽  
Gastric Glands ◽  
Oxyntic Mucosa ◽  
No Donor

We have previously identified cells containing the enzyme nitric oxide (NO) synthase (NOS) in the human gastric mucosa. Moreover, we have demonstrated that endogenous and exogenous NO has been shown to decrease histamine-stimulated acid secretion in isolated human gastric glands. The present investigation aimed to further determine whether this action of NO was mediated by the activation of guanylyl cyclase (GC) and subsequent production of cGMP. Isolated gastric glands were obtained after enzymatic digestion of biopsies taken from the oxyntic mucosa of healthy volunteers. Acid secretion was assessed by measuring [14C]aminopyrine accumulation, and the concentration of cGMP was determined by radioimmunoassay. In addition, immunohistochemistry was used to examine the localization of cGMP in mucosal preparations after stimulation with the NO donor S-nitroso- N-acetylpenicillamine (SNAP). SNAP (0.1 mM) was shown to decrease acid secretion stimulated by histamine (50 μM); this effect was accompanied by an increase in cGMP production, which was histologically localized to parietal cells. The membrane-permeable cGMP analog dibuturyl-cGMP (db-cGMP; 0.1–1 mM) dose dependently inhibited acid secretion. Additionally, the effect of SNAP was prevented by preincubating the glands with the GC inhibitor 4 H-8-bromo-1,2,4-oxadiazolo[3,4-d]benz[b][1,4]oxazin-1-one (10 μM). We therefore suggest that NO in the human gastric mucosa is of physiological importance in regulating acid secretion. Furthermore, the results show that NO-induced inhibition of gastric acid secretion is a cGMP-dependent mechanism in the parietal cell involving the activation of GC.

Neuronal nitric oxide synthase: expression in rat parietal cells

2001 ◽  
Vol 280 (2) ◽  
pp. G308-G313 ◽  
Author(s):  
Shyamal Premaratne ◽  
Chun Xue ◽  
John M. McCarty ◽  
Muhammad Zaki ◽  
Robert W. McCuen ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Intracellular Signaling ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Parietal Cells ◽  
Nadph Diaphorase ◽  
Rt Pcr ◽  
Oxyntic Mucosa

Nitric oxide synthases (NOS) are enzymes that catalyze the generation of nitric oxide (NO) from l-arginine and require nicotinamide adenine dinucleotide phosphate (NADPH) as a cofactor. At least three isoforms of NOS have been identified: neuronal NOS (nNOS or NOS I), inducible NOS (iNOS or NOS II), and endothelial NOS (eNOS or NOS II). Recent studies implicate NO in the regulation of gastric acid secretion. The aim of the present study was to localize the cellular distribution and characterize the isoform of NOS present in oxyntic mucosa. Oxyntic mucosal segments from rat stomach were stained by the NADPH-diaphorase reaction and with isoform-specific NOS antibodies. The expression of NOS in isolated, highly enriched (>98%) rat parietal cells was examined by immunohistochemistry, Western blot analysis, and RT-PCR. In oxyntic mucosa, histochemical staining revealed NADPH-diaphorase and nNOS immunoreactivity in cells in the midportion of the glands, which were identified as parietal cells in hematoxylin and eosin-stained step sections. In isolated parietal cells, decisive evidence for nNOS expression was obtained by specific immunohistochemistry, Western blotting, and RT-PCR. Cloning and sequence analysis of the PCR product confirmed it to be nNOS (100% identity). Expression of nNOS in parietal cells suggests that endogenous NO, acting as an intracellular signaling molecule, may participate in the regulation of gastric acid secretion.

scholarly journals Activation of Secretagogue Independent Gastric Acid Secretion via Endothelial Nitric Oxide Synthase Stimulation in Rats

2017 ◽  
Vol 44 (4) ◽  
pp. 1606-1615 ◽  
Author(s):  
Alice Miriam Kitay ◽  
Alexander Link ◽  
John P. Geibel
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Sodium Salt ◽  
Proton Extrusion ◽  
No Donor ◽  
Salt Hydrate ◽  
Oxide Synthase

Background/Aims: L-arginine is an important mediator of cell division, wound healing, and immune function. It can be transformed by the nitric oxide synthase (NOS) to nitric oxide (NO), an important cell signaling molecule. Recent studies from our laboratory demonstrate specific effects of L-arginine (10mM) exposure on gastric acid secretion in rat parietal cells. Methods: Studies were performed with isolated gastric glands and the pH sensitive dye BCECF-AM +/- L-arginine to examine its effects on acid secretion. The direct NO-donor diethylamine NONOate sodium salt hydrate, was also used while monitoring intracellular pH. The specific inhibitor of the intracellular NO signal cascade ODQ was also used. Results: We found that gastric proton extrusion was activated with application of L-arginine (10mM), in a separate series when L-arginine (10mM) + L-NAME (30µM) were added there was no acid secretion. Addition of the NO-donor diethylamine NONOate sodium salt hydrate (10µM) also induced acid secretion. When the selective sGC-inhibitor ODQ was added with NONOate we did not observe acid secretion. Conclusion: We conclude that L-arginine is a novel secretagogue, which can mediate gastric acid secretion. Furthermore, the intake of L-arginine causes direct activation of the H+, K+ ATPase and increased proton extrusion from parietal cells resulting in the increased risk for acid-related diseases. The NO/sGC/cGMP pathway has never been described as a possible intracellular mechanism for H+, K+ ATPase activation before and presents a completely new scientific finding. Moreover, our studies demonstrate a novel role for L-NAME to effectively eliminate NOS induced acid secretion and thereby reducing the risk for L-arginine inducible ulcer disease.

scholarly journals Immunocytochemical identification of low-affinity NTS2 neurotensin receptors in parietal cells of human gastric mucosa

2006 ◽  
Vol 191 (1) ◽  
pp. 121-128 ◽  
Author(s):  
Stefan Schulz ◽  
Christoph Röcken ◽  
Matthias P A Ebert ◽  
Solveig Schulz
Keyword(s):  
Plasma Membrane ◽  
Gastric Mucosa ◽  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Parietal Cells ◽  
Neuroendocrine Cells ◽  
Target Cells ◽  
Human Gastric Mucosa ◽  
Western Blots

The biological effects of neurotensin (NT) are mediated by two distinct G protein-coupled receptors, NTS1 and NTS2. Although it is well established that neurotensin inhibits gastric acid secretion in man, the plasma membrane receptor mediating these effects has not been visualized yet. We developed and characterized a novel antipeptide antibody to the carboxy-terminal region of the human NTS2 receptor. The cellular and subcellular distribution of NTS2 receptors was evaluated in various human gastrointestinal tissues. Specificity of the antiserum was demonstrated by (1) detection of a broadband migrating at Mr 90 000–100 000 in Western blots of membranes from NTS2-expressing tissues; (2) cell-surface staining of NTS2-transfected cells; (3) translocation of NTS2 receptor immunostaining after agonist exposure; and (4) abolition of tissue immunostaining by preadsorbtion of the antibody with its immunizing peptide. In the gastrointestinal tract, NTS2 receptor immunoreactivity was highly abundant in parietal cells of the gastric mucosa, in neuroendocrine cells of the stomach small and large intestine, and in cells of the exocrine pancreas. NTS2 receptors were clearly located in the plasma membrane and uniformly present on nearly all target cells. The presence of NTS2 receptors was rarely detected in human tumors. This is the first localization of NTS2 receptors in human formalin-fixed, paraffin-embedded tissues at the cellular level. The abundant expression of low-affinity NTS2 receptors on the plasma membrane of human parietal cells provides a morphological substrate for the direct inhibition of gastric acid secretion observed after i.v. administration of neurotensin.

scholarly journals Facilitatory effect of nitric oxide (NO) donor on gastric acid secretion in the isolated mouse whole stomach

1998 ◽  
Vol 76 ◽  
pp. 123
Author(s):  
Ko Hasebe ◽  
Syunji Horie ◽  
Shizuko Tsuchiya ◽  
Shingo Yano ◽  
Kazuo Watanabe
Keyword(s):  
Nitric Oxide ◽  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Facilitatory Effect ◽  
No Donor

scholarly journals Nitric oxide-an endogenous inhibitor of gastric acid secretion in isolated human gastric glands

2004 ◽  
Vol 4 (1) ◽  
Author(s):  
Anna Berg ◽  
Stefan Redeen ◽  
Ann-Charlott Ericson ◽  
Sven Erik Sjöstrand
Keyword(s):  
Nitric Oxide ◽  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Endogenous Inhibitor ◽  
Gastric Glands

Gastrin mediates the gastric mucosal proliferative response to feeding

1996 ◽  
Vol 271 (3) ◽  
pp. G470-G476 ◽  
Author(s):  
G. V. Ohning ◽  
H. C. Wong ◽  
K. C. Lloyd ◽  
J. H. Walsh
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Pancreatic Secretion ◽  
Proliferative Response ◽  
Male Rats ◽  
Oxyntic Mucosa ◽  
Proliferative Zone ◽  
Mucosal Proliferation

The role of endogenous gastrin in oxyntic mucosal proliferation during feeding in the rat was studied by immunoneutralization with a gastrin-specific monoclonal antibody (MAb) (CURE 051091.5). The immunochemical characteristics of this antibody were characterized by competitive radioimmunoassay, and the in vivo immunoneutralizing properties were validated by measuring effects on gastric acid and pancreatic secretion. Oxyntic mucosal proliferation in response to feeding was measured in adult male rats after a 48-h fast using bromodeoxyuridine (BrdU) immunohistochemistry. Gastrin-specific MAb inhibited gastrin-17- but not pentagastrin-stimulated gastric acid secretion and had no effect on cholecystokinin (CCK)-stimulated pancreatic secretion. In contrast, a MAb specific for the common COOH-terminal pentapeptide of gastrin and CCK inhibited gastrin-17- and pentagastrin-stimulated gastric acid secretion and CCK-stimulated pancreatic secretion. Pretreatment with gastrin-specific MAb 8 h before refeeding significantly reduced by 61% the number of BrdU-labeled cells in the oxyntic mucosal proliferative zone compared with control MAb-treated rats. These results demonstrate the importance of endogenous gastrin in the proliferative response of the oxyntic mucosa to feeding in the rat.

Effect of thyroid on gastric secretion and metabolism

1961 ◽  
Vol 201 (3) ◽  
pp. 567-570 ◽  
Author(s):  
E. S. Nasset ◽  
Dale P. J. Goldsmith
Keyword(s):  
Oxygen Consumption ◽  
Gastric Mucosa ◽  
Gastric Secretion ◽  
Thyroid Hormones ◽  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Early Summer ◽  
Tissue Concentrations ◽  
Oxygen Ratio

The effect of administration of thyroid products on gastric acid secretion and metabolism was studied in dogs with gastric pouches and in gastric mucosa from rats and frogs. Whole thyroid, thyroxin, triiodothyronine, and iodinated casein generally reduced secretion in thyroidectomized dogs and in dogs with intact thyroids. The thyroid substances elevated BMR above euthyroid levels in normal dogs but not always in thyroidectomized dogs. In dogs with intact thyroids 2,4-dinitrophenol raised oxygen consumption but did not affect secretion. Whole thyroid elevated BMR in rats and frogs but did not change resting mucosal oxygen consumption. During spring and early summer thyroid feeding reduced histamine-stimulated acid secretion and mucosal oxygen consumption during secretion in frogs, but the acid-to-oxygen ratio was unaffected. These findings suggest that elevated tissue concentrations of thyroid hormones reduce the ability of the gastric mucosa to mobilize secretory energy in response to a stimulus. This effect of the thyroid hormones is apparently not directly correlated with their calorigenic properties.

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