Development of UDP-glucuronosyltransferase activity toward digitoxigenin-monodigitoxoside in neonatal rats

J. B. Watkins, C. D. Klaassen

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Glucuronidation is low or undetectable in embryonic and early fetal tissues and changes to adult levels at rates depending on the acceptor, tissue, and species. Because other data indicate there may be a specific UDP-glucuronosyltransferase (GT) in the liver of adult rats that glucuronidates digitoxigenin-monodigitoxoside (DIG), the development of GT activity in neonatal rats toward DIG was compared with that of other acceptors. Conjugation of p-nitrophenol and 1-naphthol was higher at birth and decreased to adult levels by 20 days of age. Glucuronidation of chloramphenicol, morphine, valproic acid, and bilirubin increased from birth to adult activity by 20 days of age. Conjugation of phenolphthalein, estrone, and diethylstilbestrol was low in 1-day-old rats and higher than adult in 20-day-old animals. In contrast, glucuronidation of DIG was barely detectable (9% of adult) in 20-day-old rats. The concentration of UDP-glucuronic acid was 50% of adult levels at birth and increased to adult values by 10 days of age. Administration of 3-methylcholanthrene on days 6 to 9 after birth significantly stimulated Gt activity toward 1-naphthol, p-nitrophenol, and morphine, whereas phenobarbital precociously increased conjugation of chloramphenicol, valproic acid, morphine, and diethylstilbestrol. Pregnenolone-16α-carbonitrile enhanced the development of Gt activity toward morphine, chloramphenicol, valproic acid, bilirubin, diethylstilbestrol, and estrone. Glucuronidation of DIG was not increased after 3-methylcholanthrene or phenobarbital, but could be induced after pregnenolone-16α-carbonitrile to 7% of adult values in 10-day-old rats. Thus, development of GT activity toward DIG appears to be different than that for the other acceptors, suggesting there may be a separate GT in rat liver that is responsible for the conjugation of DIG.

Original languageEnglish (US)
Pages (from-to)186-191
Number of pages6
JournalDrug Metabolism and Disposition
Volume13
Issue number2
StatePublished - 1985
Externally publishedYes

Fingerprint

Glucuronosyltransferase
Rats
Morphine
Diethylstilbestrol
Valproic Acid
Chloramphenicol
Pregnenolone Carbonitrile
Parturition
Methylcholanthrene
Estrone
Phenobarbital
Bilirubin
Liver
Phenolphthalein
Uridine Diphosphate Glucuronic Acid
Tissue
digitoxigenin monodigitoxoside
Animals
Fetus

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Development of UDP-glucuronosyltransferase activity toward digitoxigenin-monodigitoxoside in neonatal rats. / Watkins, J. B.; Klaassen, C. D.

In: Drug Metabolism and Disposition, Vol. 13, No. 2, 1985, p. 186-191.

Research output: Contribution to journalArticle

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abstract = "Glucuronidation is low or undetectable in embryonic and early fetal tissues and changes to adult levels at rates depending on the acceptor, tissue, and species. Because other data indicate there may be a specific UDP-glucuronosyltransferase (GT) in the liver of adult rats that glucuronidates digitoxigenin-monodigitoxoside (DIG), the development of GT activity in neonatal rats toward DIG was compared with that of other acceptors. Conjugation of p-nitrophenol and 1-naphthol was higher at birth and decreased to adult levels by 20 days of age. Glucuronidation of chloramphenicol, morphine, valproic acid, and bilirubin increased from birth to adult activity by 20 days of age. Conjugation of phenolphthalein, estrone, and diethylstilbestrol was low in 1-day-old rats and higher than adult in 20-day-old animals. In contrast, glucuronidation of DIG was barely detectable (9{\%} of adult) in 20-day-old rats. The concentration of UDP-glucuronic acid was 50{\%} of adult levels at birth and increased to adult values by 10 days of age. Administration of 3-methylcholanthrene on days 6 to 9 after birth significantly stimulated Gt activity toward 1-naphthol, p-nitrophenol, and morphine, whereas phenobarbital precociously increased conjugation of chloramphenicol, valproic acid, morphine, and diethylstilbestrol. Pregnenolone-16α-carbonitrile enhanced the development of Gt activity toward morphine, chloramphenicol, valproic acid, bilirubin, diethylstilbestrol, and estrone. Glucuronidation of DIG was not increased after 3-methylcholanthrene or phenobarbital, but could be induced after pregnenolone-16α-carbonitrile to 7{\%} of adult values in 10-day-old rats. Thus, development of GT activity toward DIG appears to be different than that for the other acceptors, suggesting there may be a separate GT in rat liver that is responsible for the conjugation of DIG.",
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