Selective up-regulation of NMDA-NR1 receptor expression in myenteric plexus after TNBS induced colitis in rats.
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-NR1 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
NR1-exon 5 (N1) and NR1-exon 21 (C1) appeared 14, 21 and 28 days after TNBS treatment. NR1 pan mRNA was up-regulated at 14, 21, and 28 days. The NR1-exon 22 (C2) mRNA did not show significant changes. Using 2-D western analysis, untreated control rats were found to express only NR1001 whereas TNBS treated rats expressed NR1001, NR1011, and NR1111. Immunocytochemistry demonstrated NR1-N1 and NR1-C1 to be present in the myenteric plexus of TNBS treated rats.


CONCLUSIONS
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.
Zhou
QiQi
Q
Department of Medicine, University of Florida College of Medicine, Gainesville, FL 32610, USA. qzuou@yahoo.com
Caudle
Robert M
RM
Price
Donald D
DD
Del Valle-Pinero
Arseima Y
AY
Verne
G Nicholas
GN
D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D003106:Colon / Q000294:innervation* / Q000503:physiopathology*; D004195:Disease Models, Animal; D018698:Glutamic Acid / Q000378:metabolism; D018836:Inflammation Mediators; D008297:Male; D009197:Myenteric Plexus / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism; D010146:Pain / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014302:Trinitrobenzenesulfonic Acid; D015854:Up-Regulation / Q000502:physiology*; D017833:Visceral Afferents / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology
D018836:Inflammation Mediators; C409466:NR1 NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D014302:Trinitrobenzenesulfonic Acid