Faculty Collaboration Database

Alterations in N-methyl-D-aspartate receptor subunits in primary sensory neurons following acid-induced esophagitis in cats. Am J Physiol Gastrointest Liver Physiol 2009 Jan;296(1):G66-77

Date

11/01/2008

Pubmed ID

18974310

Pubmed Central ID

PMC2636931

DOI

10.1152/ajpgi.90419.2008

Scopus ID

2-s2.0-58249104041 (requires institutional sign-in at Scopus site)   18 Citations

Abstract

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.

Author List

Banerjee B, Medda BK, Zheng Y, Miller H, Miranda A, Sengupta JN, Shaker R

Authors

Banani Banerjee PhD Associate Professor in the Medicine department at Medical College of Wisconsin
Bidyut K. Medda PhD Associate Professor in the Medicine department at Medical College of Wisconsin
Adrian Miranda MD Adjunct Professor in the Pediatrics department at Medical College of Wisconsin
Jyoti N. Sengupta PhD Professor in the Medicine department at Medical College of Wisconsin
Reza Shaker MD Assoc Provost, Sr Assoc Dean, Ctr Dir, Chief, Prof in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Blotting, Western
Cats
Disease Models, Animal
Eosinophil Peroxidase
Esophagitis
Esophagus
Female
Ganglia, Spinal
Gastroesophageal Reflux
Hydrochloric Acid
Immunohistochemistry
Male
Neutrophil Infiltration
Neutrophils
Nodose Ganglion
Peroxidase
Protein Isoforms
Protein Subunits
Receptors, N-Methyl-D-Aspartate
Reverse Transcriptase Polymerase Chain Reaction
Sensory Receptor Cells
Time Factors