The effect of growth hormone releasing peptide-2 on upper gastrointestinal contractile activity and food intake in conscious dogs

J Gastroenterol. 2009;44(4):297-304. doi: 10.1007/s00535-009-0025-y. Epub 2009 Mar 7.

Abstract

Background: The aim of this study was to evaluate the effect of growth hormone releasing peptide (GHRP)-2, a synthetic ligand for the growth hormone secretagogue receptor, on upper gastrointestinal motility and food intake.

Methods: Five neurally intact dogs and five dogs with vagotomy and pyloroplasty were equipped with strain gauge force transducers on the stomach, duodenum and jejunum. GHRP-2 (0.5-10 microg/kg) was administered intravenously in neurally intact dogs in the interdigestive state and after feeding. To study the mechanism of GHRP-2-induced inhibition on postprandial contractions, various antagonists were administered intravenously prior to GHRP-2. The effect of GHRP-2 on postprandial contractions was also studied in dogs with vagotomy. GHRP-2 was also administered immediately before feeding in each group, and its effect on food intake was assessed.

Results: GHRP-2 did not evoke gastrointestinal contractions in the interdigestive state. GHRP-2 induced contractile inhibition continuing for 2-3 min in neurally intact dogs and dogs with vagotomy. This inhibitory effect was reversed by the alpha- and alpha(2)-blockers. GHRP-2 increased food intake in neurally intact dogs, but not in dogs with vagotomy.

Conclusions: These results indicate that in the upper gut GHRP-2 inhibits postprandial contractions via alpha(2)-receptors on the enteric nervous system, whereas an intact vagal nerve is necessary for a GHRP-2-induced increase in food intake.

MeSH terms

  • Animals
  • Dogs
  • Dose-Response Relationship, Drug
  • Duodenum / drug effects
  • Duodenum / metabolism
  • Eating / drug effects*
  • Enteric Nervous System / drug effects
  • Enteric Nervous System / metabolism
  • Gastric Mucosa / metabolism
  • Gastrointestinal Motility / drug effects*
  • Jejunum / drug effects
  • Jejunum / metabolism
  • Muscle Contraction / drug effects
  • Oligopeptides / administration & dosage
  • Oligopeptides / pharmacology*
  • Postprandial Period
  • Pylorus / surgery
  • Receptors, Adrenergic, alpha-2 / drug effects*
  • Receptors, Adrenergic, alpha-2 / metabolism
  • Receptors, Ghrelin / agonists
  • Stomach / drug effects
  • Vagotomy

Substances

  • Oligopeptides
  • Receptors, Adrenergic, alpha-2
  • Receptors, Ghrelin
  • growth hormone-releasing peptide-2