Shamburek R D, Schwartz C C
Department of Medicine, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.
J Lipid Res. 1993 Nov;34(11):1833-42.
Little is known about the mechanisms of: 1) biliary phosphatidylcholine (PC) secretion by the hepatocyte, 2) selectivity for biliary 1-palmitoyl-2-linoleoyl-PC (PLPC) secretion, and 3) exclusion of 1-stearoyl-2-arachidonyl-PC (SAPC) from bile. The experiments were designed to determine, in rats, whether selectivity (for PLPC and against SAPC) is influenced by bile acid hydrophobicity or secretion rate. We examined the effects of bile acid depletion and of ileal infusion of taurocholic acid, tauroursodeoxycholic acid, and taurochenodeoxycholic acid. Compared to bile acid depletion, infusion of each bile acid caused PLPC to decrease from 59% of bile PC to 48%, and SAPC to increase from 2.6% to 5%. Bile acid hydrophobicity had no effect on PC selectivity, but selectivity decreased to a moderate degree as total PC secretion increased. To determine whether selectivity is for preformed molecular species, we used a new method to isotopically label four species of hepatic PC. This was done by intravenous injection of PLPC and SAPC labeled in the linoleate (14C) and arachidonate (3H) moieties. Assuming rapid mixing of each PC species in the hepatocyte as supported by the specific activity data, bile SAPC and SLPC were derived entirely from hepatic preformed SAPC and SLPC; bile PLPC was from both preformed PLPC (55%) and an unlabeled input (45%, probably direct secretion of newly synthesized PLPC). In conclusion, the selective composition of bile PC is not related to bile acid hydrophobicity, but is partially lost as secretion increases within the physiologic range.
1)肝细胞分泌胆汁磷脂酰胆碱(PC)的机制;2)胆汁中1-棕榈酰-2-亚油酰-PC(PLPC)分泌的选择性;3)胆汁中排除1-硬脂酰-2-花生四烯酰-PC(SAPC)的机制。本实验旨在确定在大鼠中,(对PLPC的)选择性和(对SAPC的)排斥性是否受胆汁酸疏水性或分泌速率的影响。我们研究了胆汁酸耗竭以及回肠输注牛磺胆酸、牛磺熊去氧胆酸和牛磺鹅去氧胆酸的影响。与胆汁酸耗竭相比,输注每种胆汁酸都会使PLPC从胆汁PC的59%降至48%,使SAPC从2.6%增至5%。胆汁酸疏水性对PC选择性没有影响,但随着总PC分泌量增加,选择性会适度降低。为了确定选择性是否针对预先形成的分子种类,我们使用了一种新方法对四种肝脏PC进行同位素标记。这是通过静脉注射在亚油酸(14C)和花生四烯酸(3H)部分标记的PLPC和SAPC来完成的。根据比活性数据支持的肝细胞中每种PC种类的快速混合假设,胆汁中的SAPC和SLPC完全来自肝脏预先形成的SAPC和SLPC;胆汁中的PLPC则来自预先形成的PLPC(55%)和未标记的输入(45%,可能是新合成的PLPC的直接分泌)。总之,胆汁PC的选择性组成与胆汁酸疏水性无关,但在生理范围内随着分泌增加会部分丧失。