| Gastro protective properties of the novel prostone SPI-8811 against acid-injured porcine mucosa. | |
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MedLine Citation:
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PMID: 23002337 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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AIM: To evaluate the protective properties of novel prostone ClC-2 agonist SPI-8811 in porcine model of gastric acid injury. METHODS: Porcine gastric mucosa was mounted in Ussing chambers and injured by bathing mucosal tissues in an HCl Ringer's solution (pH = 1.5) with or without SP1-8811 (1 μmol/L), cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor (inhibitor 172, 10 μmol/L, apical) and ClC-2 inhibitor ZnCl₂, 300 μmol/L, apical), on the apical surface of tissues. Transepithelial resistance and mucosal-to-serosal ³H-mannitol fluxes were measured over a 90-min period. Tissues were analyzed by morph metric techniques, Immunofluorescence and by western blots. RESULTS: Compared with control tissues, acid exposure decreased transepithelial electrical resistance (TER) and increased ³H-mannitol flux. Pretreatment of gastric mucosa with SPI-8811 was protective against acid-induced decreases in TER (TER, 50 Ω.cm² vs 100 Ω.cm²) and abolished increases in flux (³H-mannitol flux, 0.10 μmol/L.cm² vs 0.04 μmol/L.cm²). Evidence of histological damage in the presence of acid was markedly attenuated by SPI-0811. Immunofluorescence and western analysis for occludin revealed enhanced localization to the region of the tight junction (TJ) after treatment with SPI-8811. Pretreatment with the ClC-2 inhibitor ZnCl₂, but not the selective CFTR inhibitor 172, attenuated SPI-8811-mediated mucosal protection, suggesting a role for ClC-2. Prostone may serve both protective and reparative roles in injured tissues. CONCLUSION: ClC-2 agonist SPI-8811 stimulated enhancement of mucosal barrier function by protecting TJ protein occludin in porcine gastric mucosa and thus protected the gastric acid injury in porcine stomach. |
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Authors:
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Meghali Nighot; Adam Moeser; Ryuji Ueno; Anthony Blikslager |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: World journal of gastroenterology : WJG Volume: 18 ISSN: 1007-9327 ISO Abbreviation: World J. Gastroenterol. Publication Date: 2012 Sep |
Date Detail:
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Created Date: 2012-09-24 Completed Date: 2013-05-21 Revised Date: 2013-05-30 |
Medline Journal Info:
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Nlm Unique ID: 100883448 Medline TA: World J Gastroenterol Country: China |
Other Details:
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Languages: eng Pagination: 4684-92 Citation Subset: IM |
Affiliation:
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Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Chloride Channels / agonists*, analysis Cystic Fibrosis Transmembrane Conductance Regulator / analysis Electric Impedance Gastric Mucosa / drug effects* Mannitol / metabolism Microscopy, Fluorescence Permeability Prostaglandins / pharmacology* Swine |
| Chemical | |
Reg. No./Substance:
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0/Chloride Channels; 0/ClC-2 chloride channels; 0/Prostaglandins; 0/cobiprostone; 126880-72-6/Cystic Fibrosis Transmembrane Conductance Regulator; 69-65-8/Mannitol |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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