Cava F, Gonzalez J, Gonzalez-Buitrago J M, Muriel C, Jimenez R
General Hospital of Salamanca, Spain.
Biochem J. 1991 May 1;275 ( Pt 3)(Pt 3):591-5. doi: 10.1042/bj2750591.
A number of organic anions selectively inhibit the biliary secretion of cholesterol and phospholipids without affecting bile acid secretion. We studied the effect of cefmetazole, a third-generation cephalosporin, on biliary lipid secretion in the rat. Injection of cefmetazole at a dose of 200 mumol/kg body wt. induced a choleretic effect and a significant decrease in the biliary output of cholesterol and phospholipid, without changes in bile acid secretion. The decrease was more marked for cholesterol than for phospholipid secretion, with a significant decrease in their molar ratio in bile. The effects were apparently unrelated to an inhibition of intracellular vesicular transport because, after injection of horseradish peroxidase, both the time course and total amount secreted of the protein did not significantly differ between control animals and those receiving cefmetazole. The secretory rate of the lysosomal marker acid phosphatase was not affected by cefmetazole administration. Biliary outputs of the plasma-membrane enzymes alkaline phosphatase and gamma-glutamyltransferase were significantly decreased by the antibiotic. These results point to an effect of cefmetazole at the level of the canalicular membrane.
多种有机阴离子可选择性抑制胆固醇和磷脂的胆汁分泌，而不影响胆汁酸分泌。我们研究了第三代头孢菌素头孢美唑对大鼠胆汁脂质分泌的影响。以200μmol/kg体重的剂量注射头孢美唑可引起利胆作用，并使胆固醇和磷脂的胆汁排出量显著降低，而胆汁酸分泌无变化。胆固醇分泌的减少比磷脂分泌更明显，胆汁中它们的摩尔比显著降低。这些作用显然与细胞内囊泡运输的抑制无关，因为注射辣根过氧化物酶后，对照动物和接受头孢美唑的动物之间蛋白质分泌的时间进程和总量均无显著差异。溶酶体标记物酸性磷酸酶的分泌率不受头孢美唑给药的影响。抗生素使血浆膜酶碱性磷酸酶和γ-谷氨酰转移酶的胆汁排出量显著降低。这些结果表明头孢美唑在胆小管膜水平发挥作用。
