Enhanced intestinal absorption of oxytocin peptide analogues in the absence of pancreatic juice in pigs

The present investigation was done to study the intestinal absorption of three oxytocin peptide analogues and to elucidate the role of pancreatic juice on their absorption. In conscious chronically catheterized pigs (6-8 weeks of age) plasma concentration of the peptides, [Mpa, D-Tyr(Ethyl), Thr, Orn]-oxytocin (F314), [Mpa, D-Tyr(Ethyl), Val, D-Arg]-oxytocin (CAT), and [Mpa, D-Tyr(Ethyl), Thr, Orn, desGly, carba]-oxytocin (F327) after intraduodenal administration, during presence or diversion of the pancreatic juice via a pancreatic duct catheter, were determined by radioimmunoassay. The stability of the peptides to degradation was determined in vitro by incubation with activated pancreatic juice, chymotrypsin or trypsin, followed by reversed phase HPLC analyses. All peptides were absorbed with a bioavailability of about 0.5% in the presence of pancreatic juice, but increased to 1.0%, 2.1%, and 13.5% for F314, CAT, and F327, respectively, when the pancreatic juice was diverted from the intestine. After incubation with pancreatic juice 95% of F314, 98% of F327, and 100% of CAT was found intact. When incubated with trypsin CAT remained intact while F314 and F327 were degraded by 54% and 46%, respectively. Incubation with purified chymotrypsin did not degrade the test peptides. The results indicate that the increased absorption of peptides observed under conditions of diverted pancreatic juice cannot only be explained by the absence of pancreatic enzymes, but also by changed absorptive properties in the gastrointestinal tract.