Document Detail


Gastro protective properties of the novel prostone SPI-8811 against acid-injured porcine mucosa.
MedLine Citation:
PMID:  23002337     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Meghali Nighot; Adam Moeser; Ryuji Ueno; Anthony Blikslager
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  World journal of gastroenterology : WJG     Volume:  18     ISSN:  1007-9327     ISO Abbreviation:  World J. Gastroenterol.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-09-24     Completed Date:  2013-05-21     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  100883448     Medline TA:  World J Gastroenterol     Country:  China    
Other Details:
Languages:  eng     Pagination:  4684-92     Citation Subset:  IM    
Affiliation:
Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607, USA.
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MeSH Terms
Descriptor/Qualifier:
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:
0/Chloride Channels; 0/ClC-2 chloride channels; 0/Prostaglandins; 0/cobiprostone; 126880-72-6/Cystic Fibrosis Transmembrane Conductance Regulator; 69-65-8/Mannitol
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