Monte M J, Cava F, Esteller A, Jimenez R
Department of Physiology and Pharmacology, University of Salamanca, Spain.
Biochem J. 1989 Oct 15;263(2):513-8. doi: 10.1042/bj2630513.
The effects of sodium cyclobutyrate, a synthetic hydrocholeretic drug, on biliary lipid secretion and on the biliary outputs of several plasma-membrane enzymes were investigated in anaesthetized rats. Administration of a single oral dose of cyclobutyrol (0.72 mmol/kg body wt.) reduced biliary concentration and output of cholesterol and phospholipid. However, bile acid secretion was not significantly modified. This uncoupling effect of lipid secretion remained even when the choleretic response to the drug had ceased. It additionally led to a statistically significant decrease in the cholesterol/bile acid and phospholipid/bile acid molar ratios and in the lithogenic index of the bile. The biliary outputs of the plasma-membrane enzymes alkaline phosphatase and gamma-glutamyltransferase were markedly reduced by the drug. When cyclobutyrol was administered to rats which had been previously fed with a high-cholesterol diet, the effects of cyclobutyrol persisted, but were less marked. Our results demonstrate that the bile acid-independent choleresis induced by cyclobutyrol (related to its pharmacokinetic effect) is accompanied by a pharmacodynamic action that selectively reduces the secretion of biliary lipids. This is due to an uncoupling of the secretion of cholesterol and phospholipids from that of bile acids. Possible explanations for the biliary response to cyclobutyrol are discussed.
在麻醉大鼠中研究了合成利胆药环丁酸钠对胆汁脂质分泌以及几种质膜酶胆汁排出量的影响。单次口服环丁醇（0.72 mmol/kg体重）可降低胆汁中胆固醇和磷脂的浓度及排出量。然而，胆汁酸分泌未发生显著改变。即便对该药物的利胆反应停止后，这种脂质分泌的解偶联效应依然存在。它还导致胆汁的胆固醇/胆汁酸和磷脂/胆汁酸摩尔比以及胆汁致石指数在统计学上显著降低。该药物可显著降低质膜酶碱性磷酸酶和γ-谷氨酰转移酶的胆汁排出量。当给先前喂食高胆固醇饮食的大鼠施用环丁醇时，环丁醇的作用依然存在，但不太明显。我们的结果表明，环丁醇诱导的不依赖胆汁酸的利胆作用（与其药代动力学效应有关）伴随着一种药效学作用，即选择性降低胆汁脂质的分泌。这是由于胆固醇和磷脂的分泌与胆汁酸的分泌解偶联所致。文中讨论了对环丁醇胆汁反应的可能解释。
