The role of the hepatic endoplasmic reticulum in the biliary excretion of foreign compounds by the rat: The effect of phenobarbitone and SKF 525-A (diethylaminoethyl diphenylpropylacetate)

Phenobarbitone pretreatment of rats stimulated the biliary excretion of biphenyl, stilboestrol and phenolphthalein all of which undergo metabolism prior to excretion in the bile. However, this treatment did not aflect the biliary elimination of stilboestrol glucuronide, phenolphthalein glucuronide, succinylsulphathiazole and indocyanine green all of which are excreted unchanged. SKF 525-A which inhibited the glucuronide conjugation of stilboestrol and phenolphthalein depressed their excretion in the bile in the form of their O-glucuronides. SKF 525-A did not influence the biliary excretion of phenolphthalein glucuronide. The biliary excretion of compounds such as biphenyl, stilboestrol and phenolphthalein can be considered to occur in at least two steps: (i) metabolism and (ii) transfer of the metabolites to bile. Phenobarbitone and SKF 525-A treatment in rats influences (i) but not (ii). This suggests that although the endoplasmic reticulum is involved in the metabolism of foreign compounds it does not appear to play a role in their transfer from liver to bile.