Uptake of Glucuronides into Isolated Hepatocytes and their Effects on Glucuronide and Sulphate Conjugation

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Abstract
Uptake studies, using radioactive labeled glucuronides, 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; phenolphthalein glucuronide was bound to cellular constituents. Phenolphthalein glucuronide had an effect on the conjugation of harmol in the isolated hepatocytes when glucuronidation was markedly inhibited and sulfation slightly stimulated. The glucuronidation of 4-nitrophenol, 4-methylumbelliferone and harmol in native microsomes was inhibited by phenolphthalein glucuronide, 4-Nitrophenyl glucuronide and naphthyl glucuronide did not affect hepatocytes and microsomes. In control hepatocytes harmine was metabolized to form harmolsulfate mainly. Phenolphthalein glucuronide only affected this metabolic pattern to a minor extent. In hepatocytes from phenobarbital-treated rats, where the rate of harmine metabolism is increased about 5 .times. and the main metabolite is harmol glucuronide, phenolphthalein glucuronide inhibited the formation of the conjugate with a concomitant increase in free harmol.