Document Detail


Phosphodiesterase isozymes involved in regulating acid secretion in the isolated mouse stomach.
MedLine Citation:
PMID:  20388963     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The effect of subtype-selective phosphodiesterase (PDE) inhibitors on acid secretion was examined in mouse stomachs to investigate which PDE isozymes are involved in the local regulation of this secretion. Male DDY mice were used after 18 h fasting. An isolated stomach was incubated in an organ bath containing buffered solution gassed with 95% O(2)/5% CO(2), while the lumen was perfused with unbuffered solution gassed with 100% O(2). Acid secretion was measured at pH 5.4 using a pH-stat method. Histamine or pituitary adenylate cyclase activating polypeptide (PACAP) was added to the serosal solution. PDE inhibitors were added to the serosal solution 30 min before histamine or PACAP. The secretion of acid in the isolated stomach was increased by histamine or PACAP, and these responses were totally inhibited by famotidine. IBMX alone increased basal acid secretion and significantly enhanced the acid responses to histamine and PACAP. Among the PDE inhibitors tested, only rolipram (PDE4 inhibitor) significantly increased basal acid secretion and potentiated the acid responses to histamine and PACAP. The latter peptide increased histamine release into the medium, and this response was also enhanced by rolipram. Furthermore, rolipram significantly increased cAMP production induced in the isolated stomach by histamine and PACAP. These results suggest that PDE4 is involved in the local regulation of gastric acid secretion via the degradation of cAMP and that the PDE4 inhibitor rolipram increases the secretion of acid by potentiating acid production in parietal cells and enhancing histamine release from enterochromaffin-like cells.
Authors:
S Okuda; M Honda; Y Ito; E Aihara; S Kato; S Mitsufuji; T Yoshikawa; K Takeuchi
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Publication Detail:
Type:  Comparative Study; In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of physiology and pharmacology : an official journal of the Polish Physiological Society     Volume:  60 Suppl 7     ISSN:  1899-1505     ISO Abbreviation:  J. Physiol. Pharmacol.     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2010-04-14     Completed Date:  2010-08-03     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9114501     Medline TA:  J Physiol Pharmacol     Country:  Poland    
Other Details:
Languages:  eng     Pagination:  183-90     Citation Subset:  IM    
Affiliation:
Division of Pathological Sciences, Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Yamashina, Japan.
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MeSH Terms
Descriptor/Qualifier:
1-Methyl-3-isobutylxanthine / pharmacology
3',5'-Cyclic-AMP Phosphodiesterases / antagonists & inhibitors,  physiology*
Animals
Cyclic AMP / metabolism
Dose-Response Relationship, Drug
Famotidine / pharmacology
Gastric Acid / secretion*
Gastric Mucosa / drug effects,  metabolism,  secretion
Histamine / analysis,  pharmacology
Histamine Agonists / pharmacology
Histamine Antagonists / pharmacology
Histamine Release / drug effects
Isoenzymes / antagonists & inhibitors,  physiology
Male
Mice
Organ Specificity
Perfusion / methods
Phosphodiesterase Inhibitors / pharmacology*
Pituitary Adenylate Cyclase-Activating Polypeptide / agonists,  antagonists & inhibitors,  pharmacology
Rolipram / pharmacology
Stomach / drug effects,  enzymology*,  metabolism
Time Factors
Chemical
Reg. No./Substance:
0/Histamine Agonists; 0/Histamine Antagonists; 0/Isoenzymes; 0/Phosphodiesterase Inhibitors; 0/Pituitary Adenylate Cyclase-Activating Polypeptide; 28822-58-4/1-Methyl-3-isobutylxanthine; 51-45-6/Histamine; 60-92-4/Cyclic AMP; 61413-54-5/Rolipram; 76824-35-6/Famotidine; EC 3.1.4.17/3',5'-Cyclic-AMP Phosphodiesterases

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


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