Abstract
Biliary excretion of lithocholate-3-sulfate is markedly impaired in EHBR. To examine the mechanism of biliary lithocholate-3-sulfate excretion in EHBR, the effects of colchicine treatment, a vesicular transport inhibitor, and infusion of taurocholate and organic anions were studied in EHBR and Sprague-Dawley rats. Colchicine treatment and taurocholate infusion had no effect on biliary lithocholate-3-sulfate excretion in EHBR, suggesting that biliary lithocholate-3-sulfate excretion is not mediated by the vesicular transport or by the bile acid excretory pathway. In control Sprague-Dawley rats, both sulfobromophthalein and dibromosulfophthalein infusion inhibited biliary lithocholate-3-sulfate excretion. In contrast, in EHBR dibromosulfophthalein infusion inhibited biliary lithocholate-3-sulfate excretion but BSP infusion did not. Indocyanine green and pravastatin infusion did not affect biliary lithocholate-3-sulfate excretion but pravastatin infusion had no effect in EHBR. These findings indicate that, whether physiologically important or not, two or more excretory pathways for organic anions exist at the canalicular membrane other than the ATP-dependent one.
Similar content being viewed by others
References
Takikawa H, Sano N, Narita T, Uchida Y, Yamanaka M, Horie T, Mikami T, Tagaya O: Biliary excretion of bile acid conjugates in a hyperbilirubinemic mutant Sprague-Dawley rat. Hepatology 14:352–360, 1991
Kurisu H, Kamisaka K, Koyo T, Yamasugi S, Igarashi H, Maezawa H, Uesugi T, Tagaya O: Organic anion transport study in mutant rats with autosomal recessive conjugated hyperbilirubinemia. Life Sci 49:1003–1011, 1991
Hosokawa S, Tagaya O, Mikami T, Mikami T, No50-zaki Y, Kawaguchi A, Yamatsu K, Shamoto M: A new rat mutant with chronic conjugated hyperbilirubinemia and renal glomerular lesions. Lab Anim Sci 42:27–34, 1992
Takikawa H, Sano N, Minagawa K, Yamanaka M: Effect of ursodeoxycholate, its glucuronide and disulfate and β-muricholate on biliary bicarbonate concentration and biliary lipid excretion. J Hepatol 15:77–84, 1992
Sano N, Takikawa H, Yamanaka M: Estradiol-17β-glucuronide-induced cholestasis. Effects of ursodeoxycholate-3-O-glucuronide and 3,7-disulfate. J Hepatol 17:241–246, 1993
Takikawa H, Sano N, Wako Y, Yamanaka M: Effects of organic anions and bile acids on biliary lipid excretion in hyperbilirubinemic mutant Sprague-Dawley rats. J Hepatol 17:247–252, 1993
Takikawa H, Minagawa K, Sano N, Yamanaka M: Lithocholate-3-O-glucuronide-induced cholestasis. A study with congenital hyperbilirubinemic rats and effects of ursodeoxycholate conjugates. Dig Dis Sci 38:1543–1548, 1993
Sathirakul K, Suzuki H, Yasuda K, Hanano M, Tagaya O, Horie T, Sugiyama Y: Kinetic analysis of hepatobiliary transport of organic anions in Eisai hyperbilirubinemic mutant rats (EHBR). J Pharmacol Exp Ther 265:1301–1312, 1993
Jansen PLM, Peters WH, Lamers WH: Hereditary chronic hyperbilirubinemia in mutant rats caused by defective hepatic anion transport. Hepatology 5:573–579, 1985
Kuipers F, Enserink M, Havinga R, van der Steen AdBM, Hardonk MJ, Fevery J, Vonk RJ: Separate transport systems for biliary secretion of sulfated and unsulfated bile acids in the rat. J Clin Invest 81:1593–1599, 1988
Fernandez-Checa J, Takikawa H, Horie T, Ookhtens M, Kaplowitz N: Canalicular transport of reduced glutathione in normal and mutant Eisai hyperbilirubinemic rats. J Biol Chem 267:1667–1673, 1992
Adachi Y, Kobayashi H, Kurumi Y, Shouji M, Kitano M, Yamamoto T: ATP-dependent taurocholate transport by rat liver canalicular membrane vesicles. Hepatology 14:655–659, 1991
Nishida T, Gatmaitan Z, Che M, Arias IM: Rat liver canalicular membrane vesicles contain an ATP-dependent bile acid transport system. Proc Natl Acad Sci USA 88:6590–6594, 1991
Müller M, Ishikawa T, Berger U, Klünemann C, Lucka L, Schreyer A, Kannicht C, Reutter W, Kurz G, Keppler D: ATP-dependent transport of taurocholate across the hepatocyte canalicular membrane mediated by a 110-kDa glycoprotein binding ATP and bile salt. J Biol Chem 266:18920–18926, 1991
Kast C, Stieger B, Winternalter KH, Meier PJ: Hepatocellular transport of bile acids. Evidence for distinct subcellular localization of electrogenic and ATP-dependent taurocholate transport in rat hepatocytes. J Biol Chem 269:5179–5186, 1994
Kitamura T, Jansen P, Hardenbrook C, Kamimoto U, Gatmaitan Z, Arias IM: Defective ATP-dependent canalicular transport of organic anions in mutant (TR−) rats with conjugated hyperbilirubinemia. Proc Natl Acad Sci USA 87:3557–3561, 1990
Kobayashi K, Sogame Y, Hara H, Hayashi K: Mechanism of glutathioneS-conjugate transport in canalicular and basolateral rat liver plasma membranes. J Biol Chem 265:7737–7741, 1990
Ishikawa T, Müller M, Klünemann C, Schaub T, Keppler D: ATP-dependent primary active transport of cysteinyl leukotrienes across liver canalicular membrane. Role of the ATP-dependent transport system for glutathione conjugates. J Biol Chem 265:19279–19286, 1990
Kobayashi K, Komatsu S, Nishi T, Hara H, Hayashi K: ATP-dependent transport for glucuronides in canalicular plasma membrane vesicles. Biochem Biophys Res Commun 176:622–626, 1991
Clarenburg R, Kao CC: Shared and separate pathways for biliary excretion of bilirubin and BSP in rats. Am J Physiol 225:192–220, 1973
Mahu J-L, Duvaldestin P, Dhemeaux D, Berthelot P: Biliary transport of cholephilic dyes: Evidence for two different pathways. Am J Physiol 232:E445-E450, 1977
Sathirakul K, Suzuki H, Yamada T, Hanano M, Sugiyama Y: Multiple transport systems for organic anions across the bile canalicular membrane. J Pharmacol Exp Ther 268:65–73, 1994
Adachi Y, Kobayashi H, Kurumi Y, Shouji M, Kitano M, Yamamoto T: Bilirubin diglucuronide transport by rat liver canalicular membrane vesicles: Stimulation by bicarbonate ion. Hepatology 14:1251–1258, 1991
Suchy FJ, Balistreri WF, Hung J, Miller P, Garfield SA: Intracellular bile acid transport in rat liver as visualized by electron microscope autoradiography using a bile acid analogue. Am J Physiol 245:G681-G689, 1983
Lamri Y, Roda A, Dumont M, Feldmann G, Erlinger S: Immunoperoxidase localization of bile salts in rat liver cells. Evidence for a role of the Golgi apparatus in bile acid transport. J Clin Invest 82:1173–1182, 1988
Dumont M, D'Hont C, Durand-Schneider A-M, Legrand-Defretin V, Feldmann G, Erlinger S: Inhibition by colchicine of biliary secretion of diethylmaleate in the rat: Evidence for microtubular-dependent vesicular transport. Hepatology 14:10–15, 1991
Takikawa H, Sano N, Ohki H, Yamanaka M: Comparison of biliary excretion of lithocholate and its sulfate and glucuronide conjugates. Biochim Biophys Acta 1004:147–150, 1989
Bajwa RS, Fujimoto JM: Effect of colchicine andS,S,S-tributyl phosphorotrithioate (DEF) on the biliary excretion of sucrose, mannitol and horseradish peroxidase in the rat. Biochem Pharmacol 32:85–90, 1983
Xia Y, Lambert KJ, Schteingart CD, Gu J-J, Hofmann AF: Concentrative biliary secretion of ceftriaxone. Inhibition of lipid secretion and precipitation of calcium ceftriaxone in bile. Gastroenterology 99:454–465, 1990
Author information
Authors and Affiliations
Additional information
This study was funded in part by a Grant-in-Aid for General Scientific Research (C) 06670583 from the Japanese Ministry of Education, Science and Culture.
Rights and permissions
About this article
Cite this article
Takikawa, H., Nishikawa, K., Sano, N. et al. Mechanisms of biliary excretion of lithocholate-3-sulfate in Eisai hyperbilirubinemic rats (EHBR). Digest Dis Sci 40, 1792–1797 (1995). https://doi.org/10.1007/BF02212704
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02212704