Differences in UDP-glucuronosyltransferase activities in congenic inbred rats homozygous and heterozygous for the jaundice locus.

Abstract

The genic transfer of the jaundice locus (jj) from the Gunn rat into the inbred RHA/++ rat produced congenic inbred homozygous RHA/jj rats which lacked detectable bilirubin UDP-glucuronosyltransferase activity. Congenic inbred RHA/j+ rats contained half the activity for bilirubin of the RHA/++ strain. Constitutive activities for glucuronidation of sixteen substrates of twenty-one tested were inherited additively. Approximately seven groups were discernible based on the defect in activity for these substrates in the RHA/jj strain. Activity for 1-hydroxybenzo[a]pyrene was, after that for bilirubin, the most severely reduced (188-fold), while no differences in the glucuronidation of three androgens and of the 6-hydroxy-, 10-hydroxy-, and 11-hydroxybenzo[a]pyrenes were observed. The conjugation of other substrates was affected to an intermediate extent. Most of the twenty-one glucuronidating activities were induced by phenobarbital in the RHA/jj strain as well as in the RHA/++ and RHA/j+ strains. Activities for 9-hydroxybenzo[a]pyrene and for the 2-hydroxy- and 4-hydroxybiphenyls were induced such that the defect was overcome, and the RHA/jj had the same level of activity as the RHA/++ strain. Cytochrome p-450 content and cytochrome c reductase and aminopyrine demethylase activities were unaffected in the congenic strains. Cytochrome p-450 content and cytochrome c reductase activity were induced approximately 2.5- and 2.0-fold, respectively, by phenobarbital while aminopyrine demethylase activity was induced about 30% in each strain. The congenic inbred rats should provide a stable and reproducible genetic model for studying defective UDP-glucuronosyltransferase specified by the jaundice (jj) locus.

• Authors: P I Mackenzie, I S Owens
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 32 Issue 24 Pg. 3777-81 (Dec 15 1983) ISSN: 0006-2952 [Print] England
• PMID: 6419743 (Publication Type: Journal Article)

Chemical References

• Cytochrome P-450 Enzyme System
• Aminopyrine N-Demethylase
• NADH Dehydrogenase
• Glucuronosyltransferase

Topics

• Aminopyrine N-Demethylase (metabolism)
• Animals
• Cytochrome P-450 Enzyme System (metabolism)
• Glucuronosyltransferase (genetics, metabolism)
• Heterozygote
• Homozygote
• Jaundice (enzymology, genetics)
• Male
• Microsomes, Liver (enzymology)
• NADH Dehydrogenase (metabolism)
• Phenotype
• Rats
• Rats, Inbred Strains