Document Detail


Alterations in N-methyl-D-aspartate receptor subunits in primary sensory neurons following acid-induced esophagitis in cats.
MedLine Citation:
PMID:  18974310     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The excitatory amino acid glutamate plays an important role in the development of neuronal sensitization and the ionotropic N-methyl-d-aspartate receptor (NMDAR) is one of the major receptors involved. The objective of this study was to use a cat model of gastroesophageal reflux disease (GERD) to investigate the expression of the NR1 and NR2A subunits of NMDAR in the vagal and spinal afferent fibers innervating the esophagus. Two groups of cats (Acid-7D and PBS-7D) received 0.1 N HCl (pH 1.2) or 0.1 M PBS (pH 7.4) infusion in the esophagus (1 ml/min for 30 min/day for 7 days), respectively. NR1 splice variants (both NH(2) and COOH terminals) and NR2A in the thoracic dorsal root ganglia (DRGs), nodose ganglia (NGs), and esophagus were evaluated by RT-PCR, Western blot, and immunohistochemistry. Acid produced marked inflammation and a significant increase in eosinophil peroxidase and myeloperoxidase contents compared with PBS-infused esophagus. The NR1-4 splice variant gene exhibited a significant upregulation in DRGs and esophagus after acid infusion. In DRGs, NGs, and esophagus, acid infusion resulted in significant upregulation of NR1 and downregulation of NR2A subunit gene expression. A significant increase in NR1 polypeptide expression was observed in DRGs and NGs from Acid-7D compared with control. In conclusion, long-term acid infusion in the cat esophagus resulted in ulcerative esophagitis and differential expressions of NR1 and NR2A subunits. It is possible that these changes may in part contribute to esophageal hypersensitivity observed in reflux esophagitis.
Authors:
Banani Banerjee; Bidyut K Medda; Yue Zheng; Heather Miller; Adrian Miranda; Jyoti N Sengupta; Reza Shaker
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-10-30
Journal Detail:
Title:  American journal of physiology. Gastrointestinal and liver physiology     Volume:  296     ISSN:  0193-1857     ISO Abbreviation:  Am. J. Physiol. Gastrointest. Liver Physiol.     Publication Date:  2009 Jan 
Date Detail:
Created Date:  2008-12-30     Completed Date:  2009-02-26     Revised Date:  2010-09-21    
Medline Journal Info:
Nlm Unique ID:  100901227     Medline TA:  Am J Physiol Gastrointest Liver Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  G66-77     Citation Subset:  IM    
Affiliation:
Division of Gastroenterology and Hepatology, Medical College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, WI 53226, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blotting, Western
Cats
Disease Models, Animal
Eosinophil Peroxidase / metabolism
Esophagitis / chemically induced,  metabolism*,  pathology
Esophagus / innervation,  metabolism*,  pathology
Female
Ganglia, Spinal / metabolism*
Gastroesophageal Reflux / chemically induced,  metabolism*,  pathology
Hydrochloric Acid
Immunohistochemistry
Male
Neutrophil Infiltration
Neutrophils / enzymology
Nodose Ganglion / metabolism*
Peroxidase / metabolism
Protein Isoforms
Protein Subunits
Receptors, N-Methyl-D-Aspartate / genetics,  metabolism*
Reverse Transcriptase Polymerase Chain Reaction
Sensory Receptor Cells / metabolism*
Time Factors
Grant Support
ID/Acronym/Agency:
R01 DK062312-01A/DK/NIDDK NIH HHS; R01 DK25731/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/NR1 NMDA receptor; 0/NR2A NMDA receptor; 0/Protein Isoforms; 0/Protein Subunits; 0/Receptors, N-Methyl-D-Aspartate; 7647-01-0/Hydrochloric Acid; EC 1.11.1.-/Eosinophil Peroxidase; EC 1.11.1.7/Peroxidase
Comments/Corrections

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