title: Effect of penicillin G on the biliary excretion of cholephilic compounds in rats.
abstract: OBJECTIVE
  Penicillin G is reported to increase bile flow by increasing biliary glutathione excretion, as well as the biliary excretion of penicillin G itself. In order to study the effect of penicillin G on the hepatic excretory pathway, the effect of colchicine and genipin on the increase of biliary glutathione excretion induced by penicillin G was studied in rats. The effect of penicillin G on the biliary excretion of sulfobromophthalein and erythromycin was also studied, together with the effect of penicillin G on cholestasis induced by estradiol-17β-glucuronide.
  
  
  METHODS
  After bile duct cannulation, penicillin G was administered to rats at the rate of 0.5 μmol/min/100 g. The effect was examined of colchicine pretreatment (0.2 mg/100 g) and genipin administration (0.5 μmol/min/100 g) on biliary glutathione excretion increased by penicillin G infused at the rate of 0.5 μmol/min/100 g. The effect of penicillin G on the biliary excretion of sulfobromophthalein and erythromycin (0.2 and 0.1 μmol/min/100 g for 90 min, respectively) was studied, together with the effect of penicillin G on cholestasis induced by estradiol-17β-glucuronide (0.075 μmol/min/100 g for 20 min).
  
  
  RESULTS
  Penicillin G increased bile flow and biliary glutathione excretion, which were not inhibited by colchicine or genipin. Biliary penicillin G excretion was markedly reduced in Eisai hyperbilirubinemic rats (EHBR) and Mrp2-deficient rats. Biliary sulfobromophthalein and erythromycin excretion was unchanged by penicillin G. Cholestasis induced by estradiol-17β-glucuronide was not relieved by penicillin G.
  
  
  CONCLUSIONS
  It was shown that colchicine-sensitive vesicular transport has no role on the penicillin G-induced insertion of Mrp2 into the canalicular membrane, as has been observed with genipin. Although the choleresis of penicillin G is thought to be due to the increased biliary excretion of glutathione and penicillin G itself by Mrp2, the mechanism of Mrp2 insertion by penicillin G is thought to be partly different from that by genipin.
authors: Department of Medicine, Teikyo University School of Medicine, Itabashi-ku, Tokyo 173-8605, Japan.
authors: Masako
authors: M
authors: Fukami
authors: Atsushi
authors: A
authors: Tanka
authors: Hajime
authors: H
authors: Takikawa
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001646:Bile / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000378:metabolism*; D001826:Body Fluids / Q000378:metabolism; D004195:Disease Models, Animal; D008297:Male; D010400:Penicillin G / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000900:Anti-Bacterial Agents; D001647:Bile Acids and Salts; D010400:Penicillin G