Submitted on July 9, 2008
Revised on October 22, 2008
Accepted on October 23, 2008
Alterations in N-Methyl D-Aspartate Receptor Subunits in Primary Sensory Neurons Following Acid-induced Esophagitis in Cats
Banani Banerjee, Bidyut K. Medda1, Yue Zheng, Heather Miller, Adrian Miranda, Jyoti N Sengupta1, and Reza Shaker2*
1 Medical College of Wisconsin
2 MCW
* To whom correspondence should be addressed. E-mail: rshaker{at}mcw.edu.
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 gastroesphageal 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 0.1N HCl (pH 1.2) or 0.1M PBS (pH 7.4) infusion in the esophagus (1ml/min for 30 min/day for 7 days), respectively. NR1 splice variants (both N-terminal and C-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 EPO and MPO contents compared to PBS-infused esophagus. The NR1-4 splice variant gene exhibited a significant up-regulation in DRGs and esophagus after acid infusion. In DRGs, NGs and esophagus, acid infusion resulted in significant up-regulation of NR1 and down-regulation of NR2A subunit gene expression. A significant increase in NR1 polypeptide expression was observed in DRGs and NGs from Acid-7D compared to 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.
