The ghrelin pentapeptide inhibits the secretion of pancreatic juice in rats

Ghrelin, a 28 amino acids polypeptide was recognized as an endogenous ligand for the growth hormone secretagogue receptor. It turned out that the entire sequence of ghrelin is not necessary for performing the above-mentioned functions. It was suggested that 5 residues (Gly-Ser-Ser(n-octanoyl)-Phe, pentaghrelin) constituted functionally active part of the full-length polypeptide. Ghrelin-28 was found to inhibit pancreatic enzyme output in rats, though the effect of pentaghrelin was not studied so far. The study aimed to determine the involvement of pentaghrelin in pancreatic juice secretion in anaesthetized rats. Male Wistar rats (220 ± 20 g body weight, b. wt.) were anesthetized, the external jugular vein and common biliary-pancreatic duct were cannulated. Pentaghrelin boluses (iv, 1.2, 12, and 50 nmol kg-1 b. wt.) were injected every 30 min with or without CCK-8 infusion, duodenal mucosal CCK1 receptor blockade with tarazepide, vagotomy and capsaicin pretreatment. Pentaghrelin boluses reduced the volume of pancreatic-biliary juice, protein and trypsin outputs both under basal and CCK-8-stimulated conditions in a dose-dependent manner. However, exogenous pentaghrelin failed to affect the pancreatic secretion in rats subjected to vagotomy, capsaicin deactivation of afferents or pretreatment with Tarazepide. In conclusion, pentaghrelin may control exocrine pancreas secretion by affecting duodenal neurohormonal mechanism(s) involving CCK and vagal nerves in rats.