Role of intraduodenal proteases in plasma cholecystokinin and pancreaticobiliary responses to protein and amino acids.
OBJECTIVE
The role of small intestinal proteolytic activity in the regulation of upper gastrointestinal function in humans is poorly understood. The aim of this study was to determine the importance of proteolytic activity for protein- or amino acid-induced cholecystokinin release and pancreaticobiliary secretion.


METHODS
In 9 healthy subjects, saline was perfused intraduodenally for 3 hours either with or without the synthetic protease inhibitor camostate. During the last hour, albumin or amino acids in the same molecular composition as albumin were also perfused.


RESULTS
Perfusion with camostate, in concentrations that abolished intraduodenal proteolytic activity, had no effect on unstimulated plasma cholecystokinin concentrations or gallbladder emptying, but markedly (P < 0.05) increased unstimulated pancreatic enzyme output. Perfusion with protein distinctly stimulated cholecystokinin release, gallbladder emptying, and pancreatic enzyme output (P < 0.05). Perfusion with camostate resulted in significantly lower protein-stimulated plasma cholecystokinin, gallbladder, and pancreatic enzyme responses (P < 0.05). Perfusion with amino acids also stimulated plasma cholecystokinin, gallbladder emptying, and pancreatic enzyme output (P < 0.05). Camostate did not inhibit these values.


CONCLUSIONS
This study shows that appropriate digestion of protein is required to stimulate plasma cholecystokinin release, gallbladder emptying, and pancreatic enzyme secretion in humans.
Thimister
P W
PW
Department of Gastroenterology, University Hospital St. Radboud, Nijmegen, The Netherlands.
Hopman
W P
WP
Sloots
C E
CE
Rosenbusch
G
G
Willems
H L
HL
Trijbels
F J
FJ
Jansen
J B
JB
D000328:Adult; D000418:Albumins / Q000378:metabolism*; D000596:Amino Acids / Q000378:metabolism*; D000681:Amylases / Q000378:metabolism; D001663:Bilirubin / Q000378:metabolism; D002766:Cholecystokinin / Q000097:blood*; D002918:Chymotrypsin / Q000378:metabolism; D004386:Duodenum / Q000187:drug effects / Q000201:enzymology*; D010450:Endopeptidases / Q000502:physiology*; D004952:Esters; D005260:Female; D016670:Gabexate / Q000031:analogs & derivatives*; D005704:Gallbladder / Q000378:metabolism / Q000502:physiology*; D016473:Gallbladder Emptying; D006146:Guanidines / Q000494:pharmacology; D006801:Humans; D008297:Male; D010179:Pancreas / Q000201:enzymology / Q000378:metabolism*; D010191:Pancreatic Polypeptide / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology; D014357:Trypsin / Q000378:metabolism
D000418:Albumins; D000596:Amino Acids; D004952:Esters; D006146:Guanidines; D011480:Protease Inhibitors; C034532:camostat; D016670:Gabexate; D010191:Pancreatic Polypeptide; D002766:Cholecystokinin; D000681:Amylases; D010450:Endopeptidases; D002918:Chymotrypsin; D014357:Trypsin; D001663:Bilirubin