title: Impaired capsaicin and neurokinin-evoked colonic motility in inflammatory bowel disease.
abstract: BACKGROUND
  Inflammatory bowel disease (IBD) is associated with altered sensory and motor function in the human colon. The aim of the present study was to compare neuromuscular function in normal and IBD-affected colon in vitro, with emphasis on inhibitory enteric nerves, sensory neuropeptides and stimulation of axon collaterals.
  
  
  METHODS
  Strips of longitudinal and circular muscle were prepared following colectomy from six patients with intestinal carcinoma (mean age 64.2 +/- 4.8 years) and six patients with IBD (Crohn's disease, n = 3; ulcerative colitis, n = 3: mean age 35.8 +/- 5.7 years). Responses were measured to electrical field stimulation, potassium chloride, 1,1-dimethyl-4-phenylpiperazinium iodide, isoprenaline, calcitonin gene-related peptide (CGRP), capsaicin and neurokinin (NK)-1 and -2 receptor subtype-specific agonists, alone or after muscle precontraction.
  
  
  RESULTS
  The NK-1 and CGRP receptor-mediated relaxation was reduced in the circular (by 44%, P < 0.05) and longitudinal (by 61%, P < 0.05) muscle from IBD-affected colon, respectively. Maximal NK-2 receptor-mediated contraction was also significantly decreased in both longitudinal (71%, P < 0.001) and circular (51%, P < 0.01) muscle. Capsaicin evoked relaxation in precontracted colonic longitudinal and circular muscle; this was significantly diminished in the IBD-affected colon (by 63%, P < 0.001 and 76%, P < 0.01, respectively). Responses evoked by stimulation of enteric inhibitory nerves were not significantly altered.
  
  
  CONCLUSIONS
  Colonic muscle strips from patients with IBD exhibited impaired CGRP and NK-1 receptor-mediated relaxation and NK-2 receptor-mediated contraction. Capsaicin-activated relaxation of colonic smooth muscle is deficient in IBD-affected colon. These results suggest a discrete effect of IBD on sensory-motor coupling and tachykinin-mediated effects on colonic motility.
authors.affiliation: Department of Physiology, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Alicia S
authors.initials: AS
authors.lastname: Smith
authors.forename: Scott D
authors.initials: SD
authors.lastname: Smid
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002211:Capsaicin / Q000494:pharmacology*; D016022:Case-Control Studies; D003106:Colon / Q000187:drug effects* / Q000503:physiopathology*; D004558:Electric Stimulation; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000503:physiopathology*; D008875:Middle Aged; D015288:Neurokinin A / Q000031:analogs & derivatives* / Q000494:pharmacology; D009469:Neuromuscular Junction / Q000503:physiopathology; D010446:Peptide Fragments / Q000494:pharmacology*; D013268:Stimulation, Chemical; D009435:Synaptic Transmission / Q000502:physiology; D046509:Tissue Culture Techniques
chemical_list: D010446:Peptide Fragments; C064218:neurokinin A (4-10), beta-Ala(8)-; D015288:Neurokinin A; D002211:Capsaicin