Uptake of glucuronides into isolated hepatocytes and their effects on glucuronide and sulphate conjugation

Uptake studies, using radioactive labelled glucuronides, have demonstrated the ability of 4-nitrophenyl glucuronide and phenolphthalein glucuronide to enter isolated rat hepatocytes. Of these glucuronides 4-nitrophenyl glucuronide was distributed in a similar manner to O-methylglucose, whereas phenolphthalein glucuronide was bound to cellular constituents. Phenolphthalein glucuronide had an effect on theconjugation of harmol in the isolated hepatocytes when glucuronidation was found to be markedly inhibited and sulphation slightly stimulated. The glucuronidation of 4-nitrophenol, 4-methylumbelliferone and harmol in native microsomes was inhibited by phenolphthalein glucuronide. 4-Nitrophenyl glucuronide and also naphthyl glucuronide were without effect both in hepatocytes and microsomes. In control hepatocytes harmine was metabolized to form harmolsulphate mainly. Phenolphthalein glucuronide only affected this metabolic pattern to a minor extent. However, in hepatocytes from phenobarbital treated rats, where the rate of harmine metabolism is increased about five times and the main metabolite is harmol glucuronide, phenolphthalein glucuronide inhibited the formation of the conjugate with a concomitant increase in free harmol.