Induction of pancreatic trypsin by dietary amino acids in rats: four trypsinogen isozymes and cholecystokinin messenger RNA.

We previously demonstrated that feeding a diet containing a high level of amino acid mixture simulating casein (AA) induced an increase in pancreatic protease activities in rats. In the present study, this effect of dietary AA was further characterized with three separate experiments. These experiments (1) examined periodic changes in pancreatic and small intestinal trypsin activities after switching from a 20% (a normal nitrogen level) AA diet to a 60% AA (a high nitrogen level) diet; (2) measured the abundance of mRNA for four trypsinogen isozymes and for intestinal cholecystokinin (CCK) and secretin in rats fed 20% and 60% AA diets for 10 days compared with rats fed 20% and 60% casein diets; and (3) measured the abundance of mRNA for four trypsinogen isozymes after chronic administration of CCK. Trypsin activities were gradually increased in both the pancreas and the small intestinal lumen and reached maximum at 5 days after the switch to the 60% AA diet (Exp. 1). This result is evidence that the increase in the protease activity in the pancreas is due to enhancement of pancreatic trypsin production. In experiment 2, pancreatic trypsinogen isozymes I, II, III, and IV mRNA abundance were evaluated by the Northern blotting method using cDNA probes specific for each isozyme mRNA. Abundance of trypsinogen mRNA without trypsinogen I tended to increase in the rats fed the 60% casein diet but tended to decrease in the rats fed the 60% AA diet compared with the respective normal nitrogen level diet groups without significant difference. CCK mRNA abundance in the jejunal mucosa increased as a result of feeding the 60% casein diet, but not the 60% AA diet. Subcutaneous CCK injections (3.5 nmole/kg body weight/day, twice daily, at 8:30 am and 7:30 pm) for 10 days resulted in increased pancreatic trypsin activity, whereas the changes in mRNA of the four trypsinogen isozymes was similar between the 20% and 60% casein groups but differed between the 20% and 60% AA groups (Exp. 3). These results suggest that CCK is not involved in the induction of pancreatic trypsin that occurs with feeding of a high AA diet and that the mechanism of protease induction by dietary AA is different from that in the case of dietary protein.