Carrier-mediated entry of 4-methylumbelliferyl sulfate: characterization by the multiple-indicator dilution technique in perfused rat liver

Hepatology : Official Journal of the American Association for the Study of Liver Diseases
M ChibaK S Pang

Abstract

The hepatocellular entry of 4-methylumbelliferyl sulfate (4MUS) a highly ionized and highly bound anion capable of futile cycling, was examined in the single-pass albumin-free perfused rat liver preparation. Desulfation of 4MUS to 4-methylumbelliferone (4MU) was verified in vitro to be a low-affinity, high-capacity process (Km = 731 micromol/L; Vmax = 414 nmol min(-1) g(-1) liver). With 4MUS given to the perfused rat liver, sulfation of 4MU, the formed metabolite, was attenuated in the presence of 2,6-dichloro-4-nitrophenol (DCNP), a sulfation inhibitor, and when sulfate ion was substituted by chloride ion. 4MU sulfation, being a high-affinity system, was reduced most effectively at the lowest 4MUS concentration (15 micromol/L) used, evidenced by the increased (24%) net hepatic extraction ratio of 4MUS and reduced utilization (72%) of infused tracer 35SO4(2-) by 4MU for 4MU35S formation. Single-pass multiple indicator dilution (MID) studies were thus conducted under identical conditions (DCNP and absence of inorganic sulfate), with injection of [3H]4MUS and a set of noneliminated vascular and cellular reference indicators into the portal vein (prograde) or hepatic vein (retrograde), against varying background bulk concentration...Continue Reading

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Citations

Mar 29, 2002·Biotechnology and Bioengineering·Mark J PowersLinda G Griffith
May 21, 2004·European Journal of Drug Metabolism and Pharmacokinetics·Selma Sahin, Malcolm Rowland
Apr 25, 2007·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Selma Sahin, Malcolm Rowland
Jul 22, 2006·The Journal of Pharmacology and Experimental Therapeutics·Maciej J Zamek-GliszczynskiKim L R Brouwer

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