Des-acyl ghrelin acts by CRF type 2 receptors to disrupt fasted stomach motility in conscious rats

Gastroenterology. 2005 Jul;129(1):8-25. doi: 10.1053/j.gastro.2005.04.015.


Background & aims: Although it has been shown that des-acyl ghrelin decreases food intake and gastric emptying, no previous studies have examined the effects of des-acyl ghrelin on physiologic fed and fasted motor activity in the gastrointestinal tract.

Methods: We examined the effects of intraperitoneal (IP) administration of des-acyl ghrelin on food intake and the effects of intracerebroventricular (ICV) or intravenous (IV) administration of des-acyl ghrelin on gastroduodenal motility using freely moving conscious rat models. The brain nuclei responding to these effects were examined by c- fos immunohistochemistry of the brain sections.

Results: IP injection of des-acyl ghrelin decreased food intake, and this effect was not altered by capsaicin treatment. IP injection of des-acyl ghrelin enhanced c- fos expression in the arcuate and paraventricular nucleus but not in the nucleus of the solitary tract. Both ICV and IV injection of des-acyl ghrelin disrupted fasted motor activity in the antrum but not in the duodenum. Changes in gastric motility induced by IV injection of des-acyl ghrelin were completely antagonized by ICV injection of a selective corticotropin-releasing factor (CRF) 2 receptor antagonist; however, the CRF 1 receptor antagonist had no effects.

Conclusions: The results suggest that des-acyl ghrelin decreases food intake and disrupts the fasted motor activity of the antrum in freely moving conscious rats. Peripheral des-acyl ghrelin may induce this function by direct activation of brain receptor by crossing the blood-brain barrier but not by the activation of vagal afferent pathways. In the brain, CRF 2 receptor, but not CRF 1 receptor, is involved in this action.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aniline Compounds / pharmacology
  • Animals
  • Capsaicin / pharmacology
  • Consciousness
  • Corticotropin-Releasing Hormone / pharmacology
  • Eating / drug effects
  • Fasting
  • Gastric Emptying / drug effects*
  • Ghrelin
  • Injections, Intravenous
  • Injections, Intraventricular
  • Male
  • Neuroprotective Agents / pharmacology
  • Paraventricular Hypothalamic Nucleus / drug effects
  • Paraventricular Hypothalamic Nucleus / metabolism
  • Peptide Fragments / pharmacology
  • Peptide Hormones / metabolism*
  • Peptide Hormones / pharmacology*
  • Proto-Oncogene Proteins c-fos / metabolism
  • Pyrimidines / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, Corticotropin-Releasing Hormone / antagonists & inhibitors
  • Receptors, Corticotropin-Releasing Hormone / metabolism*
  • Vagotomy, Truncal
  • Vagus Nerve / drug effects
  • Vagus Nerve / physiology


  • 2-methyl-4-(N-propyl-N-cycloproanemethylamino)-5-chloro-6-(2,4,6-trichloranilino)pyrimidine
  • Aniline Compounds
  • CRF receptor type 2
  • Ghrelin
  • Neuroprotective Agents
  • Peptide Fragments
  • Peptide Hormones
  • Proto-Oncogene Proteins c-fos
  • Pyrimidines
  • Receptors, Corticotropin-Releasing Hormone
  • antisauvagine 30
  • ghrelin, des-n-octanoyl
  • astressin
  • CRF receptor type 1
  • Corticotropin-Releasing Hormone
  • Capsaicin