Effect of intraduodenal bile salt on pancreaticobiliary responses to bombesin and to cholecystokinin in humans.
Bile salts modulate postprandial gallbladder emptying and pancreatic enzyme secretion, possibly by interfering with plasma cholecystokinin (CCK) responses. The regulatory role of bile salts in the absence of nutrients from the gut is poorly understood. Therefore, we studied the effect of intraduodenal sodium chenodeoxycholate on bombesin (BBS)- or CCK-stimulated plasma CCK levels, plasma pancreatic polypeptide levels, gallbladder motility, and pancreatic enzyme secretion. In a crossover design, saline without or with chenodeoxycholate was perfused intraduodenally for 3 hours in healthy volunteers. During the last hour, either BBS (n = 9) or CCK (n = 10) was infused intravenously. Chenodeoxycholate inhibited BBS-stimulated gallbladder emptying from 59% +/- 4% to 34% +/- 6% (P <.05) and intraduodenal bilirubin output from 41 +/- 9 to 21 +/- 5 micromol/h (P <.05), but it increased integrated plasma CCK levels from 157 +/- 19 to 184 +/- 19 pmol/L. 60 min (P =.01). Similarly, chenodeoxycholate administration inhibited gallbladder emptying and bilirubin output in response to intravenous CCK. Chenodeoxycholate also tended to reduce pancreatic polypeptide release and intraduodenal amylase output in response to intravenous BBS or CCK. It is concluded that intraduodenal chenodeoxycholate administration inhibits BBS- or CCK-stimulated gallbladder emptying, probably by diminishing target organ sensitivity to circulating CCK.
Thimister
P W
PW
Department of Gastroenterology and Hepatology, University Hospital Nijmegen, Nijmegen, the Netherlands.
Hopman
W P
WP
Tangerman
A
A
Rosenbusch
G
G
Willems
H L
HL
Jansen
J B
JB
D000293:Adolescent; D000328:Adult; D001647:Bile Acids and Salts / Q000378:metabolism; D001652:Bile Ducts / Q000187:drug effects*; D001663:Bilirubin / Q000378:metabolism; D001839:Bombesin / Q000494:pharmacology*; D002635:Chenodeoxycholic Acid / Q000008:administration & dosage* / Q000494:pharmacology; D002756:Cholagogues and Choleretics / Q000008:administration & dosage* / Q000494:pharmacology; D002766:Cholecystokinin / Q000097:blood / Q000494:pharmacology*; D004386:Duodenum / Q000378:metabolism / Q000502:physiology*; D005260:Female; D005704:Gallbladder / Q000033:anatomy & histology / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000187:drug effects* / Q000201:enzymology; D010191:Pancreatic Polypeptide / Q000097:blood
D001647:Bile Acids and Salts; D002756:Cholagogues and Choleretics; D002635:Chenodeoxycholic Acid; D010191:Pancreatic Polypeptide; D002766:Cholecystokinin; D001839:Bombesin; D001663:Bilirubin