Contrasting effects of ghrelin and des-acyl ghrelin on the lumbo-sacral defecation center and regulation of colorectal motility in rats

H. Hirayama, T. Shiina, T. Shima, H. Kuramoto, T. Takewaki, J. B. Furness, Y. Shimizu

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Background We have previously demonstrated that a centrally penetrant ghrelin receptor agonist enhances colorectal motility, through activation of the lumbo-sacral defecation center (L6-S1 region of the spinal cord) in rats. In the present study, we examined the effects of the native peptide and its non-acylated counterpart in eliciting this stimulatory effect on colorectal motility. Methods Rats were anesthetised with α-chloralose and ketamine, and colorectal intraluminal pressure and propelled intraluminal liquid volume were recorded in vivo. Key Results Intrathecal application of acylated ghrelin to the L6-S1 region of the spinal cord, but not intravenous application, elicited groups of phasic increases in colorectal intraluminal pressure that were associated with increased fluid output through the anal cannula. The effect was dose-dependent. The colokinetic effects of ghrelin were prevented if the pelvic nerves were severed. Reverse transcription polymerase chain reaction revealed the expression of the ghrelin and ghrelin receptor genes in the lumbo-sacral spinal cord. In contrast to acylated ghrelin, des-acyl ghrelin failed to cause changes in colorectal motility. However, when des-acyl ghrelin and ghrelin were applied simultaneously at the L6-S1 region, the ghrelin-induced enhancement of colorectal motility was significantly attenuated. Conclusion & Inferences It is concluded that acylation of the ghrelin peptide is essential to promote propulsive contractions of the colorectum and that des-acyl ghrelin opposes this effect. At most other sites of ghrelin action, des-acyl ghrelin either has no effect or it mimics ghrelin. This is the first evidence that non-acylated ghrelin opposes the action of the acylated peptide in the spinal cord.

Original languageEnglish
Pages (from-to)1124-1131
Number of pages8
JournalNeurogastroenterology and Motility
Volume22
Issue number10
DOIs
Publication statusPublished - Oct 2010
Externally publishedYes

Keywords

  • colorectal motility
  • defecation center
  • des-acyl ghrelin
  • ghrelin
  • ghrelin receptor
  • spinal cord

ASJC Scopus subject areas

  • Physiology
  • Endocrine and Autonomic Systems
  • Gastroenterology

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