Stolk M F, Van de Heijning B J, Van Erpecum K J, Verheem A, Akkermans L M, Van Berge-Henegouwen G P
Dept. of Gastroenterology, University Hospital Utrecht, The Netherlands.
Ital J Gastroenterol. 1996 Feb-Mar;28(2):105-10.
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.
餐后胆囊排空受损可能是胆固醇结晶沉淀及随后胆结石形成的一个重要因素。我们之前发现，与餐后胆囊收缩强烈（>50%空腹容量）的患者相比，餐后胆囊收缩微弱（<50%空腹容量）的胆结石患者胆囊胆汁中的胆汁盐浓度大幅升高。因此，我们研究了不同相对疏水性的各种结合型和非结合型胆汁盐对胆囊切除术中获取的胆囊肌条体外收缩性的潜在影响。将肌条与浓度为10(-8)-10(-4)M的胆汁盐孵育5分钟。测量10(-3)M乙酰胆碱的作用，并与预孵育对照值相关。所用胆汁盐按疏水性增加的顺序为：牛磺熊去氧胆酸、熊去氧胆酸、牛磺胆酸、牛磺脱氧胆酸和脱氧胆酸。熊去氧胆酸和牛磺熊去氧胆酸并未显著降低胆囊收缩性。牛磺胆酸在浓度为10(-6)M及更高时显著降低收缩性，牛磺脱氧胆酸在10(-7)M及更高时显著降低收缩性，脱氧胆酸在10(-5)M及更高时显著降低收缩性。在胆汁盐浓度为10(-4)M时，10(-3)M乙酰胆碱诱导的收缩性分别为对照的66.0±11.7%（牛磺胆酸）、50.2±6.2%（脱氧胆酸）和44.8±11.5%（牛磺脱氧胆酸）。胆汁盐的作用与其相对疏水性相关（r = -0.97；p < 0.01）。对胆囊肌条收缩性的抑制作用持续时间长，冲洗后仍存在。结果表明，生理剂量范围内的胆汁盐可抑制体外胆囊收缩。如果这种机制存在于体内，可能对胆囊运动调节具有重要意义。
