Colonic smooth muscle responses in patients with diverticular disease of the colon: effect of the NK2 receptor antagonist SR48968

Dig Liver Dis. 2004 May;36(5):348-54. doi: 10.1016/j.dld.2004.01.014.

Abstract

Background: Little is known about the pathophysiology of diverticular disease.

Aim: To compare passive and active stress and the response to carbachol of colonic smooth muscle specimens from patients with diverticular disease and patients with colon cancer. The effect of the NK2 receptor antagonist, SR48968, on electrically evoked contractions of circular muscle was also investigated.

Patients: Sigmoid colon segments were obtained from 16 patients (51-83 years) undergoing elective sigmoid resection for diverticular disease and 39 patients (50-88 years) undergoing left hemicolectomy for non-obstructive sigmoid colon cancer.

Methods: Isometric tension was measured on circular or longitudinal taenial muscle. Strips were stretched gradually to Lo (length allowing the development of optimal active tension with carbachol) and were also exposed to increasing carbachol concentrations. The effects of atropine, tetrodotoxin and SR48968 on electrically evoked (supramaximal strength, 0.3 ms, 0.1-10 Hz) contractions of circular strips from 8 patients with diverticular disease and 19 patients with colon cancer were also studied.

Results: Both passive and active stress in circular muscle strips obtained from patients with diverticular disease was higher than in patients with colon cancer (P < 0.05). Electrically evoked contractions were significantly reduced by atropine in all preparations and were virtually suppressed by combined SR48968 and atropine. Tetrodotoxin suppressed electrically evoked contractions only in patients with colon cancer, whereas a tetrodotoxin-resistant component was identified in patients with diverticular disease.

Conclusions: The changes in both passive and active stress in specimens from patients with diverticular disease may reflect circular smooth muscle dysfunction. Acetylcholine and tachykinins are the main excitatory neurotransmitters mediating electrically evoked contractions in human sigmoid colon circular muscle.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anesthetics, Local / pharmacology
  • Atropine / pharmacology
  • Benzamides / pharmacology*
  • Carbachol / pharmacology
  • Case-Control Studies
  • Cholinergic Agonists / pharmacology
  • Colon, Sigmoid / drug effects
  • Colon, Sigmoid / physiology*
  • Colonic Neoplasms / surgery
  • Diverticulitis, Colonic / physiopathology*
  • Diverticulitis, Colonic / surgery
  • Electric Stimulation
  • Female
  • Humans
  • In Vitro Techniques
  • Isometric Contraction / drug effects
  • Isometric Contraction / physiology*
  • Male
  • Middle Aged
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / physiology*
  • Parasympatholytics / pharmacology
  • Piperidines / pharmacology*
  • Receptors, Neurokinin-2 / antagonists & inhibitors
  • Stress, Mechanical
  • Tetrodotoxin / pharmacology

Substances

  • Anesthetics, Local
  • Benzamides
  • Cholinergic Agonists
  • Parasympatholytics
  • Piperidines
  • Receptors, Neurokinin-2
  • Tetrodotoxin
  • SR 48968
  • Atropine
  • Carbachol