Document Detail

Effect of volatile anesthetics on the hepatic UDP-glucuronic acid pathway in mice.
MedLine Citation:
PMID:  2167093     Owner:  NLM     Status:  MEDLINE    
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 pryophosphatase, 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.
J B Watkins; D R Engles; L V Beck
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochemical pharmacology     Volume:  40     ISSN:  0006-2952     ISO Abbreviation:  Biochem. Pharmacol.     Publication Date:  1990 Aug 
Date Detail:
Created Date:  1990-09-18     Completed Date:  1990-09-18     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0101032     Medline TA:  Biochem Pharmacol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  731-5     Citation Subset:  IM    
Pharmacology Section, Indiana University School of Medicine, Bloomington 47405.
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MeSH Terms
Anesthetics / pharmacology*
Ethers / pharmacology
Halothane / pharmacology
Isoflurane / pharmacology
Liver / drug effects,  metabolism*
Methyl Ethers*
Pyrophosphatases / analysis
Sex Factors
Urethane / pharmacology
Uridine Diphosphate Glucuronic Acid / analysis,  metabolism*
Uridine Diphosphate Sugars / metabolism*
Reg. No./Substance:
0/Anesthetics; 0/Ethers; 0/Methyl Ethers; 0/Uridine Diphosphate Sugars; 151-67-7/Halothane; 2616-64-0/Uridine Diphosphate Glucuronic Acid; 26675-46-7/Isoflurane; 28523-86-6/sevoflurane; 51-79-6/Urethane; EC 3.6.1.-/Pyrophosphatases; EC pyrophosphatase

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