Kinetics of the formation and secretion of the aniline metabolite 4-aminophenol and its conjugates by isolated rat hepatocytes.
The rates of secretion of 4-aminophenol and its sulphate and glucuronide conjugate were determined in cultures of rat hepatocytes with aniline and 4-aminophenol as substrates. When 4-aminophenol (300 microM) was used as substrate, 4-aminophenol disappeared from the medium within 30 min. Secretion of conjugates continued for more than 60 min, when 70% of the 4-aminophenol had been secreted as conjugates. At a low concn. of 4-aminophenol, the sulphate ester was the main metabolite, while secretion of the glucuronide showed a more than proportional rise ('lag phase') with increasing substrate concn. At higher concn. (greater than 300 microM) about equal amounts of both conjugates were formed. Without inorganic sulphate, sulphation of 4-aminophenol was greatly diminished and the lag phase in glucuronide secretion was not found. With 1 mM aniline as substrate up to 300 microM of conjugated 4-aminophenol was secreted with a linear time-dependence for at least two hours. With aniline as substrate the sulphate ester was the most important conjugate and lag phases in the secretion of both conjugates were minimal. Phenobarbitone pretreatment in vivo stimulated the secretion of conjugated products after incubation with aniline. No dramatic changes in the profile of the lag phases were seen. The differences in the conjugation profiles of both substrates can be explained by taking into consideration the differences in the expected intracellular concentrations.
D000627:Aminophenols / Q000378:metabolism*; D000814:Aniline Compounds / Q000378:metabolism; D000818:Animals; D007700:Kinetics; D008099:Liver / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D006899:Mixed Function Oxygenases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013379:Substrate Specificity; D013431:Sulfates
D000627:Aminophenols; D000814:Aniline Compounds; D013431:Sulfates; D006899:Mixed Function Oxygenases; C026729:4-aminophenol; C023650:aniline