DMD Bio-Rad Microplate Reader

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Rios, G. R.
Right arrow Articles by Tephly, T. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rios, G. R.
Right arrow Articles by Tephly, T. R.

Vol. 30, Issue 12, 1364-1367, December 2002

Inhibition and Active Sites of UDP-Glucuronosyltransferases 2B7 and 1A1.

Gladys R. Rios and Thomas R. Tephly

Department of Pharmacology, University of Iowa, Iowa City, Iowa

Two human UDP-glucuronosyltransferases (UGTs), UGT2B7 and UGT1A1, catalyze the glucuronidation of many endo- and xenobiotics. Although UGT1A1 uniquely catalyzes the glucuronidation of the endobiotic, bilirubin, and UGT2B7 uniquely catalyzes the glucuronidation of morphine to both the 3-0 glucuronide and the 6-0 glucuronide, both catalyze the glucuronidation of the mixed opioid agonist/antagonist buprenorphine with high efficiency. Etonitazenyl, a µ opioid receptor antagonist, was found to inhibit competitively opioid, steroid, and other substrate glucuronidation reactions catalyzed by UGT2B7. Data showing several benzodiazepines and alternative substrates interacting competitively support previous work, which indicates a single binding domain within UGT2B7. Etonitazenyl also competitively inhibited the glucuronidation of buprenorphine catalyzed by UGT1A1. However, neither etonitazenyl nor buprenorphine inhibited bilirubin glucuronidation except at very high concentrations. Therefore, it is unlikely that buprenorphine therapy for opioid or other drug addiction would influence bilirubin glucuronidation and lead to hyperbilirubenmia. Anthraflavic acid and catechol estrogen glucuronidation, catalyzed by UGT1A1, was also not inhibited by etonitazenyl or buprenorphine. Reactions catalyzed by UGT1A6 were not affected by etonitazenyl. These studies indicate that UGT2B7 has one binding site and that UGT1A1 has two or more binding sites for xenobiotics and endobiotics.

Copyright © 2002 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 Drug Metab. Dispos.Home page
D. Zhang, T. J. Chando, D. W. Everett, C. J. Patten, S. S. Dehal, and W. G. Humphreys
IN VITRO INHIBITION OF UDP GLUCURONOSYLTRANSFERASES BY ATAZANAVIR AND OTHER HIV PROTEASE INHIBITORS AND THE RELATIONSHIP OF THIS PROPERTY TO IN VIVO BILIRUBIN GLUCURONIDATION
Drug Metab. Dispos., November 1, 2005; 33(11): 1729 - 1739.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
J. A. Williams, R. Hyland, B. C. Jones, D. A. Smith, S. Hurst, T. C. Goosen, V. Peterkin, J. R. Koup, and S. E. Ball
DRUG-DRUG INTERACTIONS FOR UDP-GLUCURONOSYLTRANSFERASE SUBSTRATES: A PHARMACOKINETIC EXPLANATION FOR TYPICALLY OBSERVED LOW EXPOSURE (AUCI/AUC) RATIOS
Drug Metab. Dispos., November 1, 2004; 32(11): 1201 - 1208.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
D. Zhang, W. Zhao, V. A. Roongta, J. G. Mitroka, L. J. Klunk, and M. Zhu
AMIDE N-GLUCURONIDATION OF MAXIPOST CATALYZED BY UDP-GLUCURONOSYLTRANSFERASE 2B7 IN HUMANS
Drug Metab. Dispos., May 1, 2004; 32(5): 545 - 551.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
V. Uchaipichat, P. I. Mackenzie, X.-H. Guo, D. Gardner-Stephen, A. Galetin, J. B. Houston, and J. O. Miners
HUMAN UDP-GLUCURONOSYLTRANSFERASES: ISOFORM SELECTIVITY AND KINETICS OF 4-METHYLUMBELLIFERONE AND 1-NAPHTHOL GLUCURONIDATION, EFFECTS OF ORGANIC SOLVENTS, AND INHIBITION BY DICLOFENAC AND PROBENECID
Drug Metab. Dispos., April 1, 2004; 32(4): 413 - 423.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
C. Girard, O. Barbier, G. Veilleux, M. El-Alfy, and A. Belanger
Human Uridine Diphosphate-Glucuronosyltransferase UGT2B7 Conjugates Mineralocorticoid and Glucocorticoid Metabolites
Endocrinology, June 1, 2003; 144(6): 2659 - 2668.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2002 by the American Society for Pharmacology and Experimental Therapeutics.