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Nitric oxide inhibits gastric acid secretion by increasing intraparietal cell levels of cGMP in isolated human gastric glands.
MedLine Citation:
PMID:  16099867     Owner:  NLM     Status:  MEDLINE    
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 [(14)C]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 microM); 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 4H-8-bromo-1,2,4-oxadiazolo[3,4-d]benz[b][1,4]oxazin-1-one (10 microM). 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.
Anna Berg; Stefan Redéen; Magnus Grenegård; Ann-Charlott Ericson; Sven Erik Sjöstrand
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-08-11
Journal Detail:
Title:  American journal of physiology. Gastrointestinal and liver physiology     Volume:  289     ISSN:  0193-1857     ISO Abbreviation:  Am. J. Physiol. Gastrointest. Liver Physiol.     Publication Date:  2005 Dec 
Date Detail:
Created Date:  2005-11-15     Completed Date:  2005-12-19     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  100901227     Medline TA:  Am J Physiol Gastrointest Liver Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  G1061-6     Citation Subset:  IM    
Div. of Cell Biology, Dept. of Biomedicine and Surgery, Linköping University, Sweden.
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MeSH Terms
Cyclic GMP / metabolism*
Dibutyryl Cyclic GMP / pharmacology
Gastric Acid / secretion*
Guanylate Cyclase / antagonists & inhibitors
Histamine / pharmacology
Histamine Antagonists / pharmacology
Nitric Oxide / physiology*
Oxadiazoles / pharmacology
Oxazines / pharmacology
Parietal Cells, Gastric / drug effects,  metabolism*
S-Nitroso-N-Acetylpenicillamine / pharmacology
Reg. No./Substance:
0/Histamine Antagonists; 0/NS 2028; 0/Oxadiazoles; 0/Oxazines; 10102-43-9/Nitric Oxide; 32266-35-6/Dibutyryl Cyclic GMP; 51-45-6/Histamine; 7665-99-8/Cyclic GMP; 79032-48-7/S-Nitroso-N-Acetylpenicillamine; EC Cyclase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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