Guanidinated casein hydrolysate stimulates pancreatic secretagogue release by direct action to the intestine in rats.
Previously, we observed that pancreatic exocrine secretion was strongly enhanced after duodenal administration of guanidinated casein peptic hydrolysate (HGC) in rats with chronic bile-pancreatic juice (BPJ) diversion. Using a perifusion system of isolated dispersed rat intestinal mucosal cells, we investigated whether this phenomenon depends on a direct effect of protein on the intestine to release pancreatic secretagogues, such as cholecystokinin (CCK). Amylase release from isolated pancreatic acini was used as an assay to measure CCK or other pancreatic secretagogues in the effluents. Mucosal effluent with HGC stimulated amylase release from acini with or without soybean trypsin inhibitor (SBTI). Perifused effluent with low-concentrated SBTI did not stimulate amylase release. These results indicate that HGC stimulates release of pancreatic secretagogue from the intestinal mucosal cells independent of remaining trypsin activity in the isolated mucosa. Effluents with intact casein, its peptic digest, and homoarginine, which is a unique amino acid contained in HGC, were unable to stimulate amylase release from acini. Effluent with a high concentration of SBTI, which is rich in arginine residues, stimulated amylase release, but not with the same tryptic inhibitory effect of lima bean trypsin inhibitor, which is poor in arginine residues. These findings suggest that guanidyl residues in protein structure are responsible for release of pancreatic secretagogues from isolated intestinal mucosal cells. Finally, the increment of amylase release from pancreatic acini in response to the perifused effluent with HGC was eliminated in acini treated with a potent CCK antagonist, FK480. We conclude that in rats with BPJ diversion, HGC stimulates CCK release from the intestine by direct action on intestinal mucosa.
Nishi
T
T
Department of Bioscience and Chemistry, Faculty of Agriculture, Hokkaido University, Sapporo, Japan. nishi@chem.agr.hokudai.ac.jp
Hara
H
H
Kasai
T
T
D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D001646:Bile / Q000502:physiology; D002364:Caseins / Q000494:pharmacology*; D004044:Dietary Proteins / Q000494:pharmacology*; D004386:Duodenum; D019791:Guanidine / Q000378:metabolism* / Q000494:pharmacology; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D010189:Pancreatic Juice / Q000502:physiology; D010477:Perfusion; D010940:Plant Proteins / Q000494:pharmacology; D011492:Protein Hydrolysates / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014360:Trypsin Inhibitor, Kunitz Soybean / Q000494:pharmacology; D014361:Trypsin Inhibitors / Q000494:pharmacology
D000596:Amino Acids; D002364:Caseins; D004044:Dietary Proteins; D010940:Plant Proteins; D011492:Protein Hydrolysates; D014361:Trypsin Inhibitors; C025398:protease inhibitor protein, Phaseolus lunatus; C026375:trypticase-soy broth; D014360:Trypsin Inhibitor, Kunitz Soybean; D019791:Guanidine