Effect of bile salt binding or protease inactivation on plasma cholecystokinin and gallbladder responses to bombesin.
OBJECTIVE
Bombesin-stimulated plasma cholecystokinin levels decrease after an initial increase despite continuous infusion of bombesin. The aim of this study was to determine if a feedback mechanism, mediated by bile salts or proteolytic enzymes, is responsible for this decline.


METHODS
Bombesin (1.0 ng.kg-1.min-1) was infused into volunteers for 180 minutes on separate occasions. Cholestyramine, colestipol, camostate, or saline were perfused intraduodenally during the second hour of the tests. Cholestyramine was also administered without infusion of bombesin.


RESULTS
Colestipol and cholestyramine, dependent on their bile salt-binding capacity, markedly enhanced (P < 0.05) bombesin-stimulated plasma cholecystokinin from 2.1 +/- 0.5 pmol/L to 6.4 +/- 2.2 pmol/L and 12.1 +/- 3.3 pmol/L (P < 0.05 vs. colestipol), respectively, and further decreased gallbladder volume (P < 0.05) from 9.4 +/- 1.6 mL to 2.0 +/- 0.4 mL and 2.2 +/- 0.5 mL, respectively. The protease inhibitor camostate had no effect. Bile salt precipitation also enhanced plasma pancreatic polypeptide responses (P < 0.01) but did not alter gastrin responses. Plasma cholecystokinin responses to cholestyramine without bombesin infusion varied considerably, but increments were highly correlated to decreases in gallbladder volume (r = 0.91; P < 0.005).


CONCLUSIONS
Bile salt sequestration but not protease inactivation enhances plasma cholecystokinin and gallbladder responses to bombesin infusion in humans.
Department of Gastroenterology, University Hospital, Nijmegen, The Netherlands.
P W
PW
Thimister
W P
WP
Hopman
C E
CE
Sloots
G
G
Rosenbusch
A
A
Tangerman
H L
HL
Willems
C B
CB
Lamers
J B
JB
Jansen
D000328:Adult; D001647:Bile Acids and Salts / Q000378:metabolism*; D001839:Bombesin / Q000494:pharmacology*; D002766:Cholecystokinin / Q000097:blood*; D002792:Cholestyramine Resin / Q000494:pharmacology; D003084:Colestipol / Q000494:pharmacology; D010450:Endopeptidases / Q000378:metabolism*; D004789:Enzyme Activation; D004952:Esters; D005246:Feedback; D005260:Female; D016670:Gabexate / Q000031:analogs & derivatives*; D005704:Gallbladder / Q000187:drug effects* / Q000502:physiology; D005755:Gastrins / Q000097:blood; D006146:Guanidines / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D011480:Protease Inhibitors / Q000494:pharmacology; D011485:Protein Binding
D001647:Bile Acids and Salts; D004952:Esters; D005755:Gastrins; D006146:Guanidines; D011480:Protease Inhibitors; C034532:camostat; D002792:Cholestyramine Resin; D016670:Gabexate; D002766:Cholecystokinin; D010450:Endopeptidases; D003084:Colestipol; D001839:Bombesin