Inhibitory effect of bile salts on gallbladder smooth muscle contractility in the guinea pig in vitro.
OBJECTIVE
Impaired gallbladder emptying occurs in patients undergoing bile salt therapy for cholesterol gallstone dissolution and in patients with cirrhosis who have elevated serum bile salt concentrations. To determine if bile salts directly inhibit gallbladder contractility, isometric contraction of the guinea pig gallbladder was examined in vitro.


METHODS
Contractile responses to cholecystokinin (CCK), bethanechol, KCI, and field stimulation were constructed alone and in the presence of selected bile salts: taurodeoxycholate (TDC), taurochenodeoxycholate, taurocholate, and tauroursodeoxycholate (TUDC).


RESULTS
More hydrophobic bile salts, such as TDC (as low as 5 micromol/L), concentration-dependently depressed (P < 0.05) both CCK- and field stimulation-induced gallbladder contractions. More hydrophilic bile salts, such as TUDC, only caused a modest depression up to a concentration of 500 micromol/L. When 5 or 50 micromol/L of TUDC was added to the organ bath before the application of equalmolar TDC, the TDC-induced impaired gallbladder contractility was reversed. Thus, this inhibitory effect on gallbladder contraction depended on the hydrophobicity of bile salts and was also specific for certain stimuli such as CCK and field stimulation (mediated by cholinergic nerves, being abolished by atropine and tetrodotoxin).


CONCLUSIONS
Such direct bile salt inhibition of CCK- and cholinergic nerve-induced gallbladder contraction may contribute to the deteriorating gallbladder emptying in patients undergoing bile salt therapy for stone dissolution and in cirrhotic patients who are at risk for gallstone formation.
Xu
Q W
QW
Department of Medicine, Faculty of Medicine, University of Calgary, Alberta, Canada.
Freedman
S M
SM
Shaffer
E A
EA
D000818:Animals; D018723:Bethanechol / Q000494:pharmacology; D001647:Bile Acids and Salts / Q000494:pharmacology*; D002766:Cholecystokinin / Q000494:pharmacology; D004558:Electric Stimulation; D005704:Gallbladder / Q000187:drug effects* / Q000502:physiology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D011189:Potassium Chloride / Q000494:pharmacology
D001647:Bile Acids and Salts; D018723:Bethanechol; D011189:Potassium Chloride; D002766:Cholecystokinin; D007770:L-Lactate Dehydrogenase