Enteropancreatic circulation of digestive enzymes does not exist in the rat

Abstract

The hypothesis of an enteropancreatic circulation^1–3, that digestive enzymes are absorbed intact across the intestinal epithelium, are circulated through the bloodstream and rese-creted by the exocrine pancreas, has generated considerable discussion^4–6 and has been accepted by a number of medical scientists^7–9. However, the data presented in support of this hypothesis do not demonstrate with certainty that labelled proteins introduced into the bathing medium^1,3, intestinal tract^1,2 or bloodstream² appear unmodified in pancreatic juice. We have now critically examined that part of the hypothesis which proposes that pancreatic secretory proteins are taken up from the bloodstream and secreted intact into the pancreatic juice. Injection of ³⁵S-methionine-labelled rat pancreatic amylase into the blood circulation of unanaesthetized rats resulted in the appearance of radioactivity in all exocrine pancreatic proteins and showed a distribution which was indistinguishable from that following the intravenous administration of ³⁵S-methionine. These findings are not consistent with the direct transport of amylase from the blood circulation to the pancreatic ductal lumen, but are consistent with metabolic degradation of the polypeptide probe and reutilization of the free ³⁵S-methionine for the synthesis and secretion of the entire complement of pancreatic exocrine proteins. In contrast, analysis of bile by similar methods indicated the presence of a haematobiliary pathway, which accounted for the excretion of 0.8% of exocrine pancreatic proteins injected into the blood circulation.