Intracolonic Administration of the TRPA1 Agonist Allyl Isothiocyanate Stimulates Colonic Motility and Defecation in Conscious Dogs

J Gastrointest Surg. 2015 Jul;19(7):1342-9. doi: 10.1007/s11605-015-2813-4. Epub 2015 Apr 9.

Abstract

Background: The aim of the present study was to investigate the effects of the intracolonic transient receptor potential (TRP) A1 agonist allyl isothiocyanate (AITC) on colonic motility and defecation.

Methods: The effects of AITC administered into the proximal colonic lumen on colonic motility and defecation were studied in neurally intact dogs equipped with strain-gauge force transducers on the colon, with or without various antagonists. Effects of intracolonic AITC were also studied in dogs with either transection/re-anastomosis (T/R) between the proximal and middle colon and complete extrinsic denervation of an ileocolonic segment.

Results: AITC increased colonic motility and induced giant migrating contractions (GMCs) with defecations in 75% of experiments in neurally intact dogs. These effects were inhibited by atropine, hexamethonium, ondansetron, and HC-030031 but unaltered by capsazepine. In dogs with T/R, the increase in colonic motility was inhibited in the middle-distal colon. In dogs with extrinsic denervation, the increase in colonic motility in the distal colon was decreased.

Conclusions: Intracolonic AITC stimulates colonic motility and defecation via cholinergic, serotonergic, and TRPA1 pathways. Continuity of colonic enteric neurons plays an essential role in the intracolonic AITC-induced colonic motor response, while extrinsic nerves are important in occurrence and propagation of GMCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetanilides / pharmacology
  • Anastomosis, Surgical
  • Animals
  • Atropine / pharmacology
  • Capsaicin / analogs & derivatives
  • Capsaicin / pharmacology
  • Colon / drug effects*
  • Colon / innervation
  • Colon / physiology
  • Colon / surgery
  • Defecation / drug effects*
  • Denervation
  • Dogs
  • Enteric Nervous System / drug effects
  • Enteric Nervous System / physiology
  • Ganglionic Blockers / pharmacology
  • Gastrointestinal Motility / drug effects*
  • Hexamethonium / pharmacology
  • Ileum / innervation
  • Isothiocyanates / administration & dosage
  • Isothiocyanates / pharmacology*
  • Muscarinic Antagonists / pharmacology
  • Ondansetron / pharmacology
  • Purines / pharmacology
  • Serotonin Antagonists / pharmacology
  • Transient Receptor Potential Channels / agonists*

Substances

  • 2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide
  • Acetanilides
  • Ganglionic Blockers
  • Isothiocyanates
  • Muscarinic Antagonists
  • Purines
  • Serotonin Antagonists
  • Transient Receptor Potential Channels
  • Hexamethonium
  • Ondansetron
  • Atropine
  • allyl isothiocyanate
  • capsazepine
  • Capsaicin