Persistent alterations to enteric neural signaling in the guinea pig colon following the resolution of colitis.
Functional changes induced by inflammation persist following recovery from the inflammatory response, but the mechanisms underlying these changes are not well understood. Our aim was to investigate whether the excitability and synaptic properties of submucosal neurons remained altered 8 wk post-trinitrobenzene sulfonic acid (TNBS) treatment and to determine whether these changes were accompanied by alterations in secretory function in submucosal preparations voltage clamped in Ussing chambers. Mucosal serotonin (5-HT) release measurements and 5-HT reuptake transporter (SERT) immunohistochemistry were also performed. Eight weeks after TNBS treatment, colonic inflammation resolved, as assessed macroscopically and by myeloperoxidase assay. However, fast excitatory postsynaptic potential (fEPSP) amplitude was significantly increased in submucosal S neurons from previously inflamed colons relative to those in control tissue. In addition, fEPSPs from previously inflamed colons had a hexamethonium-insensitive component that was not evident in age-matched controls. AH neurons were hyperexcitable, had shorter action potential durations, and decreased afterhyperpolarization 8 wk following TNBS adminstration. Neuronally mediated colonic secretory function was significantly reduced after TNBS treatment, although epithelial cell signaling, as measured by responsiveness to both forskolin and bethanecol in the presence of tetrodotoxin, was comparable with control tissue. 5-HT levels and SERT immunoreactivity were comparable to controls 8 wk after the induction of inflammation, but there was an increase in glucagon-like peptide 2-immunoreactive L cells. In conclusion, sustained alterations in enteric neural signaling occur following the resolution of colitis, which are accompanied by functional changes in the absence of active inflammation.
Lomax
Alan E
AE
Gastrointestinal Diseases Research Unit, Department of Medicine, Queen's University, Kingston, Ontario, Canada.
O'Hara
Jennifer R
JR
Hyland
Niall P
NP
Mawe
Gary M
GM
Sharkey
Keith A
KA
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D018723:Bethanechol / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D002452:Cell Count; D005576:Colforsin / Q000494:pharmacology; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D017615:Enteric Nervous System / Q000503:physiopathology*; D019858:Enteroendocrine Cells / Q000737:chemistry / Q000166:cytology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D053767:Glucagon-Like Peptide 2 / Q000032:analysis; D006168:Guinea Pigs; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D019894:Peptide YY / Q000032:analysis; D009195:Peroxidase / Q000378:metabolism; D012701:Serotonin / Q000032:analysis / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000032:analysis; D013368:Submucous Plexus / Q000503:physiopathology; D013779:Tetrodotoxin / Q000494:pharmacology; D014302:Trinitrobenzenesulfonic Acid / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology
D053767:Glucagon-Like Peptide 2; D050486:Serotonin Plasma Membrane Transport Proteins; D018723:Bethanechol; D019894:Peptide YY; D005576:Colforsin; D012701:Serotonin; D013779:Tetrodotoxin; D014701:Veratridine; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase