title: Effect of bile salts on in vitro gallbladder motility: preliminary study.
abstract: Impaired postprandial gallbladder emptying may be an important factor in cholesterol crystals precipitation and subsequent gallstone formation. We previously found strongly increased bile salt concentrations in gallbladder bile of gallstone patients with weak (< 50% fasting volume) postprandial gallbladder contraction compared to patients with strong (> 50%) postprandial contraction. Therefore, we studied potential effects of various conjugated and unconjugated bile salts with different relative hydrophobicity on in vitro contractility of gallbladder muscle strips obtained at cholecystectomy. Strips were incubated 5 min with bile salt at concentrations of 10(-8)-10(-4)M. The effect of 10(-3)M acetylcholine was measured and related to preincubation control value. Bile salts used were, in order of increasing hydrophobicity: tauroursodeoxy-, ursodeoxy-, tauro-, taurodeoxy- and deoxycholate. Ursodeoxy- and tauroursodeoxycholate did not significantly reduce gallbladder contractility. Taurocholate significantly reduced contractility at concentrations of 10(-6) M and higher, taurodeoxycholate at 10(-7) M and higher and deoxycholate at 10(-5) M and higher. Contractility induced by acetylcholine 10(-3) M at a bile salt concentration of 10(-4) M was 66.0 +/- 11.7% (taurocholate), 50.2 +/- 6.2% (deoxycholate) and 44.8 +/- 11.5% (taurodeoxycholate) of control. The effect of bile salts correlated with their relative hydrophobicity (r = -0.97; p < 0.01). Suppressing effects on gallbladder muscle strip contractility were long lasting and remained after rinsing. Results show that bile salts in the physiological dose range inhibit in vitro gallbladder contraction. If this mechanism exists in vivo, it may have important implications for gallbladder motility regulation.
authors.affiliation: Dept. of Gastroenterology, University Hospital Utrecht, The Netherlands.
authors.forename: M F
authors.initials: MF
authors.lastname: Stolk
authors.forename: B J
authors.initials: BJ
authors.lastname: Van de Heijning
authors.forename: K J
authors.initials: KJ
authors.lastname: Van Erpecum
authors.forename: A
authors.initials: A
authors.lastname: Verheem
authors.forename: L M
authors.initials: LM
authors.lastname: Akkermans
authors.forename: G P
authors.initials: GP
authors.lastname: Van Berge-Henegouwen
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D001647:Bile Acids and Salts / Q000494:pharmacology*; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D005260:Female; D005704:Gallbladder / Q000187:drug effects*; D016473:Gallbladder Emptying / Q000187:drug effects*; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects
chemical_list: D001647:Bile Acids and Salts; D005765:Gastrointestinal Agents; D000109:Acetylcholine