PT - JOURNAL ARTICLE AU - N. HAMADA AU - T. GESSNER TI - EFFECT OF 3-METHYLCHOLANTHRENE PRETREATMENT ON GLUCURONIDATION AND SULFATION IN PERFUSED RAT LIVER DP - 1975 Sep 01 TA - Drug Metabolism and Disposition PG - 407--416 VI - 3 IP - 5 4099 - http://dmd.aspetjournals.org/content/3/5/407.short 4100 - http://dmd.aspetjournals.org/content/3/5/407.full SO - Drug Metab Dispos1975 Sep 01; 3 AB - The metabolism of p-nitro[14C]phenol (PNP) was studied in perfused rat liver. Metabolites were identified in perfusate and bile. The perfusion system containing 0.5 mM PNP, at the start, converted the phenol within 2 hr to p-nitrophenyl glucuronide (PNPGA), 31.4% in perfusate and 21% in bile; p-nitrophenyl sulfate (PNPS), 22% in perfusate; and p-nitrophenyl glucoside (PNPG), between 2 and 4% in perfusate. Biliary excretion of PNPS and PNPG accounted for less than 2% of PNP. An apparent maximal rate of PNPGA synthesis by the perfused liver, estimated from the rates of appearance of PNPGA in perfusate and bile, corresponded well to the glucuronyl-transferase activities determined in "native" liver homogenates. Sulfation of PNP in the perfused liver exhibited two apparent maximal rates of synthesis, as determined from the rates of appearance of the metabolite in the perfusate. A slower rate (R1) occurred when PNP concentration was between 0.13 and 0.5 mM, and a faster rate (R2) when PNP was approximately between 0.025 and 0.13 mM in the perfusate. Possible significance of these findings is discussed. Pretreatment of rats with 3-methylcholanthrene (3MC) increased the apparent maximal rate of PNPGA production by the perfused liver by a factor of 1.7, and biliary excretion of PNPGA by a factor of 1.5. The latter increase was attributed to the increased rate of synthesis of the glucuronide rather than to an increase in the biliary transport maximum, since the 3MC treatment produced no significant effect on the biliary excretion of performed PNPGA added to the perfusate. The 3MC pretreatment increased 1.5-fold the rate of sulfation of PNP, as judged by the increase in R2. Copyright © 1975 by The American Society for Pharmacology and Experimental Therapeutics