Hepatic uptake of p-nitrophenyl sulfate by transporter that acetaminophen sulfate shares for uptake: sulfate moiety as a vector for metabolite transport.
Hepatic uptake of the sulfate conjugate of p-nitrophenol (p-NPsul) has been studied. Uptake clearance of p-NPsul by isolated rat hepatocytes was dependent on p-NPsul concentration, suggesting carrier-mediated transport. The uptake of p-NPsul by isolated rat hepatocytes was inhibited by acetaminophen sulfate (APAPsul), the uptake of which had been previously reported to be inhibited by p-NPsul. The hepatic uptake of p-NPsul was also inhibited by bromosulfophthalein (BSP) or dibromosulfophthalein (DBSP), which had been reported to inhibit hepatic uptake of APAPsul in the previous study. These inhibitory effects were observed in isolated perfused liver experiments as well as in isolated hepatocyte experiments. Therefore, it was concluded that hepatic uptake of p-NPsul was mediated by a transporter, which mediates hepatic uptake of APAPsul as well as BSP or DBSP. It is suggested that sulfate moiety may have a key role as a vector for the hepatic transport of sulfate conjugate metabolites. Interaction between sulfate conjugate metabolites in hepatic uptake may also be expected.
Sakuma-Sawada
N
N
Department of Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Science, Hachioji, Japan.
Iida
S
S
Mizuma
T
T
Hayashi
M
M
Awazu
S
S
D000082:Acetaminophen / Q000494:pharmacology*; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001693:Biological Transport, Active; D002478:Cells, Cultured / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009578:Nitrobenzenes / Q000378:metabolism* / Q000493:pharmacokinetics; D011339:Probenecid / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013431:Sulfates / Q000494:pharmacology*; D013448:Sulfobromophthalein / Q000494:pharmacology
D018712:Analgesics, Non-Narcotic; D009578:Nitrobenzenes; D013431:Sulfates; D013448:Sulfobromophthalein; C023379:4-nitrophenyl sulfate; C012479:dibromosulphthalein; D000082:Acetaminophen; D011339:Probenecid