Effect of human pancreatic polypeptide and its C-terminal hexapeptide on pancreatic secretion in man and in the dog.

Abstract

Human pancreatic polypeptide (HPP) and its C-terminal hexapeptide (HP-PP) were infused intravenously in graded doses into healthy human subjects and dogs with chronic pancreatic fistula during submaximal stimulation with secretin. Plasma levels of PP were measured by radioimmunoassay, and pancreatic volume flow and bicarbonate and protein outputs were monitored. PP and HP-PP in humans did not affect secretion-induced volume flow or bicarbonate secretion, but at the highest doses it reduced the protein outputs. In dogs both HPP and HP-PP inhibited dose-dependently the pancreatic volume flow and bicarbonate and protein outputs. There was a linear correlation between the dose of HPP infused and the increments in plasma PP levels in these experiments. The inhibition of pancreatic secretion occurred at doses of exogenous HPP which produced blood plasma PP concentrations not significantly different from those normally seen after a meat meal. We conclude that there is a marked difference in the effect of HPP on the exocrine pancreas in man and the dog, that PP may play a role as a physiological inhibitor of pancreatic protein secretion in man and of both bicarbonate and protein secretion in the dog, and that the effect of HPP on the exocrine pancreas can be mimicked by its C-terminal hexapeptide.