AJP - Gastrointestinal and Liver Physiology, Vol 265, Issue 3 445-G452, Copyright © 1993 by American Physiological Society

ARTICLES

Preserved organic anion transport in mutant TR- rats with a hepatobiliary secretion defect

P. L. Jansen, J. W. van Klinken, M. van Gelder, R. Ottenhoff and R. P. Elferink
Department of Hepatology and Gastroenterology, Academic Medical Center, Amsterdam, The Netherlands.

The in vivo biliary secretion of a number of organic anions in mutant TR- rats was studied. The secretion of bilirubin glucuronide (BG), the glutathione conjugate of bromosulfophthalein, dibromosulfophthalein, and indocyanine green was reduced to 2, 15, 50, and 75% of normal, respectively. Surprisingly, the secretion of bilirubin ditaurate (BDT) was entirely normal under these conditions. In isolated TR- rat liver perfusion experiments (recirculating setup), the hepatobiliary secretion of BG and BDT was reduced to 1 and 50% of normal, respectively. There was considerable residual concentrative transport of BDT under these conditions (bile-to-perfusate concentration ratio of 190 +/- 60; normal, 730 +/- 480), whereas for BG the concentration step was completely abolished (bile-to-perfusate concentration ratio of 1.3 +/- 1.0; normal, 60 +/- 40). In a single-pass isolated TR- rat liver perfusion study, BDT secretion after bolus administration (1 mumol) was abnormal; the peak secretion was retarded to 20 min after injection (normal 7.5 min), and the secretion rate was decreased to 19% of normal. BDT, as an organic dianion, is a substrate for the "canalicular multispecific organic anion transporter" (cMOAT), a carrier protein that is defective in TR- rats. Its considerable residual secretion in certain experimental conditions suggests the preservation of a low-affinity pathway for secretion of some cMOAT substrates in TR- rats.

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