Effect of volatile anesthetics on the hepatic UDP-glucuronic acid pathway in mice

John B. Watkins, Drew R. Engles, Lyle V. Beck

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Large, rapid decreases in hepatic UDP-glucuronic acid concentrations occur in rats following exposure to myriad chemicals. In fact, 80% reductions in UDP-glucuronic acid occur within minutes after exposure to inhalation anesthetics. The present study was designed to determine whether this decrease in hepatic UDP-glucuronic acid may be due to (a) a decrease in the precursor UDP-glucose; (b) decreased activity of UDP-glucose dehydrogenase, which oxidizes UDP-glucose to UDP-glucuronic acid; (c) increased activity of UDP-glucuronosyltransferases; or (d) increased activity of nucleotide pyrophosphatase, which degrades UDP-glucuronic acid to glucuronic acid-1-phosphate. Exposure to halothane, isoflurane and sevoflurane decreased UDP-glucuronic acid concentrations by 40-52% as compared to that in unanesthetized control mice. No sex-dependent or anesthetic-induced effects of UDP-glucose levels and the activities of UDP-glucose dehydrogenase and UDP-glucuronosyltransferase were observed. Nucleotide pyrophosphatase activity was increased by 47-65% in female mice after inhalation of halothane, isoflurane and sevoflurane. The apparent Vmax for hydrolysis of 4-nitrophenol thymidine 5′-monophosphate ester by nucleotide pyrophosphatase was increased by 56-80% in female mice, whereas the apparent Km was unchanged. These alterations in nucleotide pyrophosphate kinetics may be responsible, in part, for the marked decrease of hepatic UDP-glucuronic acid concentrations by the volatile anesthetics.

Original languageEnglish
Pages (from-to)731-735
Number of pages5
JournalBiochemical Pharmacology
Volume40
Issue number4
DOIs
StatePublished - Aug 15 1990

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Uridine Diphosphate Glucuronic Acid
Anesthetics
nucleotide pyrophosphatase
Uridine Diphosphate Glucose
Liver
Uridine Diphosphate Glucose Dehydrogenase
Glucuronosyltransferase
Isoflurane
Halothane
Thymidine Monophosphate
Inhalation Anesthetics
Glucuronic Acid
Thymidine
Inhalation
Rats
Hydrolysis
Esters
Nucleotides
Phosphates
Kinetics

ASJC Scopus subject areas

  • Pharmacology

Cite this

Effect of volatile anesthetics on the hepatic UDP-glucuronic acid pathway in mice. / Watkins, John B.; Engles, Drew R.; Beck, Lyle V.

In: Biochemical Pharmacology, Vol. 40, No. 4, 15.08.1990, p. 731-735.

Research output: Contribution to journalArticle

Watkins, John B. ; Engles, Drew R. ; Beck, Lyle V. / Effect of volatile anesthetics on the hepatic UDP-glucuronic acid pathway in mice. In: Biochemical Pharmacology. 1990 ; Vol. 40, No. 4. pp. 731-735.
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