Effects of CCK-8 in combination with natural or synthetic secretin on amylase, lipase, trypsin, and chymotrypsin secretion in rats

In the present study, we examined the interaction between CCK-8 and natural or synthetic secretin on pancreatic enzyme secretion. On anaesthetized rats, a proximal duodenal segment was continuously perfused with saline and amylase, lipase, trypsin, and chymotrypsin were determined in the perfusate. Neither during iv saline nor during iv secretin (natural or synthetic) at doses of 0.01, 0.05, or 0.1 CU/kg/h, any of the four enzymes changed significantly from basal values over a period of 100 min. Iv CCK-8 at stepwise increasing doses of 5, 10, and 20 pmol/kg/h elicited a significant increase of all four enzymes at the medium dose, with a further increase of amylase and trypsin, but not lipase and chymotrypsin at 20 pmol/kg/h. The addition of secretin at all 3 doses potentiated CCK-induced trypsin output. The effects of natural secretin were more pronounced than those of the synthetic peptide. Secretin significantly increased amylase secretion over basal at the lowest dose of CCK-8 (5 pmol/kg/h) that by itself had no effect on amylase release. Only the higher doses of natural but not synthetic secretin augmented lipase secretion during the lowest dose of CCK-8. Both forms of secretin had no further stimulatory effect on CCK-induced chymotrypsin secretion. The present data demonstrate that, first, in rats a potentiation of CCK-8-induced enzyme secretion by low doses of secretin is different for the four enzymes, which suggests a differential regulatory action of these two intestinal hormones on pancreatic enzyme release. Second, the different effects of natural secretin may represent those of contaminants suggesting that only synthetic secretin should be employed in future studies of this peptide on pancreatic enzyme secretion.