Lillienau J, Crombie D L, Munoz J, Longmire-Cook S J, Hagey L R, Hofmann A F
Department of Physiological Chemistry, University of Lund, Sweden.
Gastroenterology. 1993 Jan;104(1):38-46. doi: 10.1016/0016-5085(93)90833-x.
Active transport of conjugated bile acids by ileal enterocytes is a key mechanism for conservation of the bile acid pool. Experiments were performed to determine whether such transport is regulated by substrate load.
Using anesthetized biliary fistula guinea pigs or rats, the ileum was perfused with ursodeoxycholyltaurine at a concentration causing maximal ileal transport of this bile acid; absorption was assessed by biliary recovery. Before ileal perfusion, animals ingested one of three diets: chow, chow with added conjugated bile acid, or chow with added cholestyramine.
In the guinea pig, ingestion of a taurocholate-enriched diet resulted in a 75% decrease in the absorption rate of ursodeoxycholyltaurine. Similar results were obtained with cholylsarcosine (a deconjugation-dehydroxylation resistant analogue) or with chenodeoxycholylglycine, the endogenous bile acid of the guinea pig. In contrast, cholestyramine ingestion caused an increase in ursodeoxycholyltaurine absorption. In the rat, cholyltaurine or cholylsarcosine ingestion also caused decreased ileal transport. In the guinea pig, maximal down-regulation of active ileal bile acid transport occurred after 2-3 days of bile acid feeding; up-regulation required 3-4 days.
Bile acid metabolism is regulated by feedback inhibition of active ileal transport in addition to the well-established feedback inhibition of bile acid biosynthesis in the liver. Together, these two regulatory mechanisms ensure constancy of bile acid secretion.
回肠肠细胞对结合型胆汁酸的主动转运是胆汁酸池保存的关键机制。进行实验以确定这种转运是否受底物负荷调节。
使用麻醉的胆瘘豚鼠或大鼠，以能引起该胆汁酸最大回肠转运的浓度用熊去氧胆酰牛磺酸灌注回肠；通过胆汁回收评估吸收情况。在回肠灌注前，动物摄入三种饮食之一：普通饲料、添加结合型胆汁酸的普通饲料或添加消胆胺的普通饲料。
在豚鼠中，摄入富含牛磺胆酸盐的饮食导致熊去氧胆酰牛磺酸的吸收速率降低75%。用胆酰肌氨酸（一种抗去结合-去羟基化的类似物）或豚鼠内源性胆汁酸鹅去氧胆酰甘氨酸也得到了类似结果。相反，摄入消胆胺导致熊去氧胆酰牛磺酸吸收增加。在大鼠中，摄入胆酰牛磺酸或胆酰肌氨酸也导致回肠转运减少。在豚鼠中，胆汁酸喂养2 - 3天后，回肠胆汁酸主动转运出现最大程度的下调；上调需要3 - 4天。
除了肝脏中已确立的胆汁酸生物合成的反馈抑制外，胆汁酸代谢还受回肠主动转运的反馈抑制调节。这两种调节机制共同确保胆汁酸分泌的恒定。
