Canine pancreatic response to intestinally perfused oligopeptides

Abstract

Although older work indicated that luminal peptides are stimulants of pancreatic secretion, these earlier experiments were performed with crude peptide mixtures containing amino acids that are also known stimulants. Furthermore, no information was provided about size or composition of stimulating peptides. For this reason, the problem was reinvestigated with commercially synthesized oligopeptides in dogs equipped with chronic gastric and pancreatic fistulas. Synthetic peptides at 30 mM concentrations were perfused into the proximal bowel when luminal pancreatic proteases were reduced to undetectable concentrations and dogs were receiving intravenous exogenous secretin infusions. Increases in pancreatic outputs of protein and bicarbonate were measured. Of the peptides tested, only glycylphenylalanine, glycyltryptophan, and phenylalanylglycine stimulated, whereas both di- and triglycine were without effect. It was concluded that some, but not all, oligopeptides in the gut lumen are stimulants of pancreatic secretion.

Calcium‐sensing receptor mediates phenylalanine‐induced cholecystokinin secretion in enteroendocrine STC‐1 cells

“…1) at normal extracellular Ca 2+ concentrations (1.2 m m ). The effective concentration of Phe (20 m m ) in these cells corresponds to the Phe concentrations (8–50 m m ) that were found to stimulate CCK or pancreatic secretion in human and dog studies [2–5]. CCK secretion induced by 10 and 20 m m Phe was significantly enhanced by increasing the extracellular Ca 2+ concentration from 1.2 to 3.0 m m .…”

“…It is well known that Phe and Trp are potent stimulants of CCK secretion in humans and dogs [2][3][4][5]. However, the underlying mechanism by which these amino acids trigger CCK secretion remains unclear.…”

“…Fatty acids, dietary protein and peptides are potent stimulants [1]. Aromatic amino acids (phenylalanine and tryptophan) are also known to stimulate CCK and pancreatic secretion in humans and dogs [2–5]. The cellular mechanism by which these amino acids stimulate CCK secretion in enteroendocrine cells is still unclear.…”

Pancreatic Secretory Response to Intestinal Stimulants: A Review

“…In humans, only essential amino acids have been found to stimulate pancreatic secretion when perfused intestinally; of these, only methionine, valine, and phenylalanine were effective stimulants when given alone (17). In dogs, intestinal infusion of peptides and amino acids caused a low-volume, enzyme-rich pancreatic juice (18,19). The amino acids tryptophan and phenylalanine are particularly effective and have been found to stimulate pancreatic enzyme secretion to the same extent in dogs (20, 21).…”

“…Konturek et al (22), however, noted that of the 13 different amino acids which stimulated canine pancreatic enzyme secretion, tryptophan and phenylalanine, lysine and methionine were the most potent. Intestinal perfusion with dipeptides containing phenylalanine or tryptophan (19) and oligopeptides containing four or more amino acids (18) also stimulated pancreatic enzyme secretion in dogs. Intact protein is not a stimulus of pancreatic secretion in dogs (18) but in rats (23).…”