Selective up-regulation of NMDA-NRI receptor expression in myenteric plexus after TNBS induced colitis in rats

Abstract

Background: N-methyl-D-aspartic acid (NMDA) spinal cord receptors play an important role in the development of hyperalgesia following inflammation. It is unclear, however, if changes in NMDA subunit receptor gene expression in the colonic myenteric plexus are associated with colonic inflammation. We investigated regulation of NMDA-NRI receptor gene expression in TNBS induced colitis in rats. Male Sprague-Dawley rats (150 g-250 g) were treated with 20 mg trinitrobenzene sulfonic acid (TNBS) diluted in 50% ethanol. The agents were delivered with a 24 gauge catheter inserted into the lumen of the colon. The animals were sacrificed at 2, 7, 14, 21, and 28 days after induction of the colitis, their descending colon was retrieved for reverse transcription-polymerase chain reaction; a subset of animals' distal colon was used for two-dimensional (2-D) western analysis and immunocytochemistry. Results: NRI-exon 5 (N1) and NRI-exon 21 (C1) appeared 14, 21 and 28 days after TNBS treatment. NRI pan mRNA was up-regulated at 14, 21, and 28 days. The NRI -exon 22 (C2) mRNA did not show significant changes. Using 2-D western analysis, untreated control rats were found to express only NRI001 whereas TNBS treated rats expressed NRI001, NRI011, and NRI111. Immunocytochemistry demonstrated NRI-N1 and NRI-C1 to be present in the myenteric plexus of TNBS treated rats. Conclusion: These results suggest a role for colonic myenteric plexus NMDA receptors in the development of neuronal plasticity and visceral hypersensitivity in the colon. Up-regulation of NMDA receptor subunits may reflect part of the basis for chronic visceral hypersensitivity in conditions such as post-infectious irritable bowel syndrome. © 2006 Zhou et al; licensee BioMed Central Ltd.