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

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.

Stimulatory effects of endogenous and exogenous nitric oxide on gastric acid secretion in anesthetized rats

Nitric Oxide ◽  
2005 ◽  
Vol 13 (4) ◽  
pp. 264-271 ◽  
Author(s):  
Ko Hasebe ◽  
Syunji Horie ◽  
Tohru Noji ◽  
Kazuo Watanabe ◽  
Shingo Yano
Keyword(s):  
Nitric Oxide ◽  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Anesthetized Rats ◽  
Exogenous Nitric Oxide

Involvement of endogenous nitric oxide in the inhibition by endotoxin and interleukin-1β of gastric acid secretion

1994 ◽  
Vol 9 (S1) ◽  
pp. S45-S49 ◽  
Author(s):  
J. V. ESPLUGUES ◽  
M. A. MARTÍNEZ-CUESTA ◽  
M. D. BARRACHINA ◽  
S. CALATAYUD ◽  
B. J. R. WHITTLE
Keyword(s):  
Nitric Oxide ◽  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Interleukin 1Β ◽  
Endogenous Nitric Oxide

scholarly journals Synthesis of nitric oxide in the dorsal motor nucleus of the vagus mediates the inhibition of gastric acid secretion by central bombesin

1999 ◽  
Vol 127 (7) ◽  
pp. 1603-1610 ◽  
Author(s):  
Belén Beltrán ◽  
Ma Dolores Barrachina ◽  
Asunción Méndez ◽  
Enrique Quintero ◽  
Juan V Esplugues
Keyword(s):  
Nitric Oxide ◽  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Motor Nucleus ◽  
Dorsal Motor Nucleus

Characteristics of the K+-competitive H+,K+-ATPase inhibitor AZD0865 in isolated rat gastric glands

2006 ◽  
Vol 291 (5) ◽  
pp. G838-G843 ◽  
Author(s):  
P. Kirchhoff ◽  
K. Andersson ◽  
T. Socrates ◽  
S. Sidani ◽  
O. Kosiek ◽  
...  
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Imaging System ◽  
Success Rates ◽  
Atpase Inhibitor ◽  
Gastric Glands ◽  
Ulcer Disease ◽  
Fast Acting

The gastric H+,K+-ATPase of the parietal cell is responsible for acid secretion in the stomach and is the main target in the pharmacological treatment of acid-related diseases. Omeprazole and other benzimidazole drugs, although having delayed efficacy if taken orally, have high success rates in the treatment of peptic ulcer disease. Potassium competitive acid blockers (P-CAB) compete with K+ for binding to the H+,K+-ATPase and thereby they inhibit acid secretion. In this study, the in vitro properties of AZD0865, a reversible H+,K+-ATPase inhibitor of gastric acid secretion, are described. We used a digital-imaging system and the pH sensitive dye BCECF to observe proton efflux from hand-dissected rat gastric glands. Glands were stimulated with histamine (100 μM) and exposed to a bicarbonate- and Na+-free perfusate to induce an acid load. H+,K+-ATPase inhibition was determined by calculating pHi recovery (dpH/dT) in the presence of omeprazole (10–200 μM) or AZD0865 (0.01–100 μM). The efficacies of both drugs were compared. Our data show that acid secretion is inhibited by both the proton pump inhibitor omeprazole and the P-CAB AZD0865. Complete inhibition of acid secretion by AZD0865 had a rapid onset of activation, was reversible, and occurred at a 100-fold lower dose than omeprazole (1 μM AZD0865 vs. 100 μM omeprazole). This study demonstrates that AZD0865 is a potent, fast-acting inhibitor of gastric acid secretion, effective at lower concentrations than drugs of the benzimidazole class. Therefore, these data strongly suggest that AZD0865 has great potential as a fast-acting, low-dose inhibitor of acid secretion.

scholarly journals Impairment of H+-K+-ATPase-dependent proton transport and inhibition of gastric acid secretion by ethanol

2001 ◽  
Vol 280 (6) ◽  
pp. G1331-G1340 ◽  
Author(s):  
Juan C. del Valle ◽  
María Salvatella ◽  
Irma Rossi ◽  
Ramón Andrade ◽  
Yolanda Gutiérrez ◽  
...  
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Proton Transport ◽  
Gastric Gland ◽  
Hydrolytic Activity ◽  
Gastric Glands ◽  
Isolated Gastric Glands ◽  
Low Concentrations ◽  
Camp Levels

Ethanol (1–20% vol/vol) caused a dose-dependent reduction in the basal rate of acid formation in isolated rabbit gastric glands with a calculated EC50 value of 4.5 ± 0.2%. Ethanol also reduced ATP levels in isolated gastric glands and in cultured parietal cells (EC50: 8.8 ± 0.4% and 8.5 ± 0.2%, respectively) and decreased both basal and forskolin-stimulated cAMP levels. In studies carried out in gastric gland microsomes, ethanol inhibited the hydrolytic activity of H+-K+-ATPase (EC50: 8.5 ± 0.6%), increased passive proton permeability (EC50: 7.9%), and reduced H+-K+-ATPase-dependent proton transport (EC50: 3%). Our results show that the inhibition of gastric acid secretion observed at low concentrations of ethanol (≤5%) is mainly caused by the specific impairment of H+-K+-ATPase-dependent proton transport across cell membranes rather than inhibition of the hydrolytic activity of H+-K+-ATPase, reduction in the cellular content of ATP, or increase in the passive permeability of membranes to protons, although these changes, in combination, must be relevant at concentrations of ethanol ≥7%.

Sign in / Sign up

Export Citation Format

Share Document