Colchicine inhibits taurodeoxycholate transport in pericentral but not in periportal hepatocytes.
Indirect evidence for a microtubule-dependent vesicular hepatocellular transport of bile acids has accumulated. Since inhibition of this transport by colchicine can be achieved only at high but not at low bile acid infusion rates we were wondering whether this transport pathway shows a hepatic zonation or not. To answer this question we perfused isolated rat livers antegradely or retrogradely, respectively, with unlabeled and labeled taurocholate or taurodeoxycholate. Inhibition of microtubule-dependent bile acid transport was aimed at co-infusion of colchicine. Periportal cells eliminated the likewise hydrophobic taurodeoxycholate as fast as the more hydrophilic taurocholate. In contrast, pericentral cells excreted taurodeoxycholate much slower than taurocholate. Colchicine did not change the biliary taurocholate excretion profile in periportal and pericentral cells. However, colchicine reduced significantly taurodeoxycholate excretion in pericentral but not in periportal cells. It is concluded that a microtubule-dependent vesicular, colchicine-sensitive transport pathway seems to be involved in the translocation of taurodeoxycholate in pericentral but not in periportal cells. Since such a vesicular bile acid transport is regarded to be much slower than transcellular transport by diffusion, this observation may explain the much slower excretion of hydrophobic bile acids like taurodeoxycholate in pericentral than in periportal cells under physiological conditions.
Baumgartner
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Department of Surgery, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany. baumgart@ch11.ukl.uni-freiburg.de
Baier
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Schöffel
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Farthmann
E H
EH
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D003078:Colchicine / Q000494:pharmacology*; D003902:Detergents / Q000493:pharmacokinetics; D004347:Drug Interactions; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008870:Microtubules / Q000378:metabolism; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D013657:Taurodeoxycholic Acid / Q000493:pharmacokinetics*
D003902:Detergents; D013657:Taurodeoxycholic Acid; D003078:Colchicine