CCK receptors in release of pancreatic polypeptide (PP) in dogs

Abstract

Pancreatic polypeptide (PP) is released after ingestion of protein-fat meals and following administration of some gut hormones (CCK and bombesin), but the hormonal contribution to the physiological release of PP has not been elucidated. We used specific and potent CCK-receptor antagonist, L-364,718, administered intravenously in a dose of 0.5 μmol/kg or intraduodenally in a dose of 2 μmol/kg to assess the role of CCK in the release of PP. Exogenous CCK-8 infused intravenously in gradually increasing doses (12.5–400 pmol/kg/hr) caused a dose-dependent increase in plasma PP from basal 28±4 pM to 136±18 pM, and this PP increase was completely suppressed by both intravenous and intraduodenal administration of L-364,718. Meat feeding caused a dramatic increase in plasma PP from a basal level of 26±4 pM to a peak of about 190±32 pM, and the pretreatment with intravenous or intraduodenal L-364,718 reduced this PP increase by about 60%. Duodenal perfusion with oleate (0.12–4.0 mmol/hr) or L-Trp (0.12–4.0 mmol/hr) also increased plasma PP, reaching, respectively, 180±28 pM and 76±6 pM. Pretreatment with intravenous or intraduodenal L-364,718 completely abolished the plasma PP responses to oleate and l-Trp. Bombesin (100 pmol/kglhr) raised plasma PP to the level similar to that achieved by meat feeding and L-364,718 given intravenously or intraduodenally blocked completely these plasma PP increments. L-364,718 did not affect basal pancreatic secretion but reduced by about 60% the pancreatic protein response to meat feeding and abolished completely the protein response to exogenous CCK and bombesin as well as to duodenal perfusion with oleate or l-Trp. We conclude that the plasma PP concentrations increase during the pancreatic secretion induced by endogenous (meat feeding, duodenal oleate or amino acids) and exogenous (CCK or bombesin) stimulants and that this increase involves the CCK receptors.