Stimulation of defecation in spinal cord-injured rats by a centrally acting ghrelin receptor agonist

Spinal Cord. 2011 Oct;49(10):1036-41. doi: 10.1038/sc.2011.60. Epub 2011 May 31.

Abstract

Study design: Animal proof of principle study.

Objectives: To determine whether capromorelin, a compound that causes defecation by stimulating ghrelin receptors within the lumbosacral defecation centers, is effective after spinal cord injury (SCI), and whether SCI significantly alters sensitivity to the compound.

Setting: University of Melbourne and Austin Hospital, Melbourne, Australia.

Methods: Rats were subjected to spinal cord contusion injury or were sham-operated. At 6 weeks after surgery, effects of capromorelin on blood pressure, heart rate and propulsive contractions of the colorectum were investigated.

Results: Capromorelin caused robust propulsive activity in the colorectum soon after its application. The compound was similarly effective in naïve, sham-operated and spinal cord-injured rats. Blood pressure increases caused by capromorelin were not exaggerated after SCI, and there was no evidence of phasic blood pressure increases when the colon was contracted by the compound.

Conclusion: Capromorelin is a therapeutic compound that could potentially be used to relieve constipation by triggering defecation in spinal cord-injured patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Constipation / drug therapy*
  • Constipation / etiology
  • Constipation / physiopathology*
  • Defecation / drug effects*
  • Defecation / physiology
  • Disease Models, Animal
  • Growth Hormone / metabolism
  • Male
  • Piperidines / pharmacology*
  • Pyrazoles / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Ghrelin / agonists*
  • Receptors, Ghrelin / physiology
  • Spinal Cord Injuries / complications
  • Spinal Cord Injuries / physiopathology*

Substances

  • CP 424391
  • Piperidines
  • Pyrazoles
  • Receptors, Ghrelin
  • Growth Hormone