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

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. 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 mu g/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. 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. 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.