Hayakawa T, Ng O C, Ma A, Boyer J L
Liver Center, Yale University School of Medicine, New Haven, Connecticut.
Gastroenterology. 1990 Jul;99(1):216-28. doi: 10.1016/0016-5085(90)91251-z.
The effect of taurocholate on transcytotic vesicular pathways labeled with horseradish peroxidase was assessed in isolated perfused rat liver preparations. Forty-five minutes after a horseradish peroxidase load in a recirculating system, continuous infusion of taurocholate but not taurodehydrocholate significantly increased horseradish peroxidase excretion in bile by 50% compared with controls. When horseradish peroxidase (25 mg) was pulse loaded for 1 minute in control perfusions, it appeared in bile in early (4-6 minutes) and late (20-25 minutes) peaks, the latter accounting for 90% of total horseradish peroxidase output. Taurocholate infusion significantly increased horseradish peroxidase output in both early and late peaks, whereas only a small increase in the early peak was observed with taurodehydrocholate. Colchicine pretreatment increased the early peak in bile but abolished the second peak. Electron micrographs from control livers revealed the accumulation of horseradish peroxidase-containing vesicles in pericanalicular regions at early (2 minutes) as well as late (18 minutes) periods. When a morphometric analysis of electron micrographs was performed from pericanalicular regions 2 minutes after a 1-minute pulse of horseradish peroxidase (500 mg), taurocholate but not taurodehydrocholate increased both the density and percent area of horseradish peroxidase-containing vesicles compared with controls. In contrast, colchicine pretreatment had no effect on the density of the early-appearing vesicles, although their individual sizes were reduced. Taurocholate but not taurodehydrocholate also increased the percent of tubular structures in the pericanalicular region. These findings indicate that taurocholate stimulates both early and late transcytotic vesicle pathways and therefore probably microtubule-independent vesicle pathway is present in hepatocytes that must be distinguished from paracellular routes.
在离体灌注大鼠肝脏标本中评估了牛磺胆酸盐对用辣根过氧化物酶标记的转胞吞小泡途径的影响。在循环系统中注入辣根过氧化物酶45分钟后，持续输注牛磺胆酸盐而非牛磺去氢胆酸盐，与对照组相比，胆汁中辣根过氧化物酶的排泄量显著增加了50%。在对照灌注中，当以脉冲方式注入辣根过氧化物酶（25毫克）1分钟时，它在胆汁中出现早期（4 - 6分钟）和晚期（20 - 25分钟）峰值，后者占辣根过氧化物酶总输出量的90%。输注牛磺胆酸盐显著增加了早期和晚期峰值时辣根过氧化物酶的输出量，而输注牛磺去氢胆酸盐时仅观察到早期峰值有小幅增加。秋水仙碱预处理增加了胆汁中的早期峰值，但消除了第二个峰值。对照肝脏的电子显微镜照片显示，在早期（2分钟）和晚期（18分钟），含辣根过氧化物酶的小泡在胆小管周围区域积累。当在注入辣根过氧化物酶（500毫克）1分钟后2分钟，对胆小管周围区域的电子显微镜照片进行形态计量分析时，与对照组相比，牛磺胆酸盐而非牛磺去氢胆酸盐增加了含辣根过氧化物酶小泡的密度和面积百分比。相反，秋水仙碱预处理对早期出现的小泡密度没有影响，尽管它们的个体大小减小了。牛磺胆酸盐而非牛磺去氢胆酸盐还增加了胆小管周围区域管状结构的百分比。这些发现表明，牛磺胆酸盐刺激早期和晚期转胞吞小泡途径，因此可能肝细胞中存在不依赖微管的小泡途径，这必须与细胞旁途径区分开来。
