| Phosphodiesterase isozymes involved in regulating acid secretion in the isolated mouse stomach. | |
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MedLine Citation:
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PMID: 20388963 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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S Okuda; M Honda; Y Ito; E Aihara; S Kato; S Mitsufuji; T Yoshikawa; K Takeuchi |
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Publication Detail:
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Type: Comparative Study; In Vitro; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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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:
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Created Date: 2010-04-14 Completed Date: 2010-08-03 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9114501 Medline TA: J Physiol Pharmacol Country: Poland |
Other Details:
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Languages: eng Pagination: 183-90 Citation Subset: IM |
Affiliation:
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Division of Pathological Sciences, Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Yamashina, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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1-Methyl-3-isobutylxanthine
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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:
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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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