T. Nishi et al., GUANIDINATED CASEIN HYDROLYSATE STIMULATES PANCREATIC SECRETAGOGUE RELEASE BY DIRECT ACTION TO THE INTESTINE IN RATS, Proceedings of the Society for Experimental Biology and Medicine, 218(4), 1998, pp. 357-364
Previously, we observed that pancreatic exocrine secretion was strongl
y enhanced after duodenal administration of guanidinated casein peptic
hydrolysate (HGC) in rats with chronic bile-pancreatic juice (BPJ) di
version. Using a perifusion system of isolated dispersed rat intestina
l mucosal cells, we investigated whether this phenomenon depends on a
direct effect of protein on the intestine to release pancreatic secret
agogues, such as cholecystokinin (CCK), Amylase release from isolated
pancreatic acini was used as an assay to measure CCK or other pancreat
ic secretagogues in the effluents, Mucosal effluent with Hoc stimulate
d amylase release from acini with or without soybean trypsin inhibitor
(SBTI), Perifused effluent with low-concentrated SBTI did not stimula
te amylase release. These results indicate that Hoc stimulates release
of pancreatic secretagogue from the intestinal mucosal cells independ
ent of remaining trypsin activity in the isolated mucosa, Effluents wi
th intact casein, its peptic digest, and homoarginine, which is a uniq
ue amino acid contained in HGC, were unable to stimulate amylase relea
se from acini. Effluent with a high concentration of SBTI, which is ri
ch in arginine residues, stimulated amylase release, but not with the
same tryptic inhibitory effect of lima bean trypsin inhibitor, which i
s poor in arginine residues. These findings suggest that guanidyl resi
dues in protein structure are responsible far release of pancreatic se
cretagogues from isolated intestinal mucosal cells. Finally, the incre
ment of amylase release from pancreatic acini in response to the perif
used effluent with HGC was eliminated in acini treated with a potent C
CK antagonist, FK480, We conclude that in rats with BPJ diversion, HGC
stimulates CCK release from the intestine by direct action on intesti
nal mucosa.