Alterations in N-methyl-D-aspartate receptor subunits in primary sensory neurons following acid-induced esophagitis in cats.
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.
Banerjee
Banani
B
Division of Gastroenterology and Hepatology, Medical College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, WI 53226, USA.
Medda
Bidyut K
BK
Zheng
Yue
Y
Miller
Heather
H
Miranda
Adrian
A
Sengupta
Jyoti N
JN
Shaker
Reza
R
D000818:Animals; D015153:Blotting, Western; D002415:Cats; D004195:Disease Models, Animal; D047209:Eosinophil Peroxidase / Q000378:metabolism; D004941:Esophagitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D004947:Esophagus / Q000294:innervation / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005727:Ganglia, Spinal / Q000378:metabolism*; D005764:Gastroesophageal Reflux / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D006851:Hydrochloric Acid; D007150:Immunohistochemistry; D008297:Male; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000201:enzymology; D009620:Nodose Ganglion / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism; D020033:Protein Isoforms; D021122:Protein Subunits; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D011984:Sensory Receptor Cells / Q000378:metabolism*; D013997:Time Factors
C409466:NR1 NMDA receptor; C120997:NR2A NMDA receptor; D020033:Protein Isoforms; D021122:Protein Subunits; D016194:Receptors, N-Methyl-D-Aspartate; D047209:Eosinophil Peroxidase; D009195:Peroxidase; D006851:Hydrochloric Acid