Hepatic, intestinal and renal transport of 1-naphthol-beta-D-glucuronide in mutant rats with hereditary-conjugated hyperbilirubinemia.
Recently, a mutant rat strain was described with a genetic defect for the biliary excretion of organic anions (TR-rats). To determine the possible heterogeneity of the transport systems in liver, intestine and kidney we investigated the transport of the anion 1-naphthol-beta-D-glucuronide (1-NG) in isolated vascularly perfused organ preparations of the rat liver, intestine and kidney of both Wistar rats and TR- rats. 1-NG was administered as such (liver and kidney experiments) or formed intracellularly from 1-naphthol (1-N) (liver and gut experiments). Independent of the type of exposure to 1-NG, the biliary excretion was considerably impaired in TR- rats. In the intestine the total appearance and the vascular/luminal distribution pattern of 1-NG were not significantly different from the values in control rats. Furthermore, no significant disturbance was found with respect to the renal clearance of 1-NG in the TR- rat when compared with the Wistar rat. Thus, the genetic defect in the TR- rat is restricted to an impaired hepatobiliary excretion of 1-NG and does not affect the excretory systems of the intestine and kidney. These results suggest that the excretion of 1-NG by the liver, intestine and kidney involves distinct organ-specific transport systems.
de Vries
M H
MH
Department of Pharmacology, Faculty of Pharmacy, University of Utrecht, The Netherlands.
Redegeld
F A
FA
Koster
A S
AS
Noordhoek
J
J
de Haan
J G
JG
Oude Elferink
R P
RP
Jansen
P L
PL
D000818:Animals; D001646:Bile / Q000378:metabolism; D005965:Glucuronates / Q000493:pharmacokinetics*; D006933:Hyperbilirubinemia, Hereditary / Q000378:metabolism*; D007421:Intestine, Small / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D011339:Probenecid / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011922:Rats, Mutant Strains; D013463:Sulfuric Acid Esters / Q000493:pharmacokinetics*; D013464:Sulfuric Acids / Q000493:pharmacokinetics*
D005965:Glucuronates; D013463:Sulfuric Acid Esters; D013464:Sulfuric Acids; C029092:naphthyl sulfate; C029091:naphthyl glucuronide; D011339:Probenecid