Human, rat and crocodile liver microsomal monooxygenase activities measured using diazepam and nifedipine: effects of CYP3A inhibitors and relationship to immunochemically detected CYP3A apoprotein.

Reilly, P. E., Mason, S. R. and Read, M. A. (1999) Human, rat and crocodile liver microsomal monooxygenase activities measured using diazepam and nifedipine: effects of CYP3A inhibitors and relationship to immunochemically detected CYP3A apoprotein.. Comparative Biochemistry and Physiology Part C: Pharmacology, Toxicology and Endocrinology, 122 2: 197-204. doi:10.1016/S0742-8413(98)10106-8


Author Reilly, P. E.
Mason, S. R.
Read, M. A.
Title Human, rat and crocodile liver microsomal monooxygenase activities measured using diazepam and nifedipine: effects of CYP3A inhibitors and relationship to immunochemically detected CYP3A apoprotein.
Journal name Comparative Biochemistry and Physiology Part C: Pharmacology, Toxicology and Endocrinology   Check publisher's open access policy
ISSN 1367-8280
1879-1093
Publication date 1999-02-01
Sub-type Article (original research)
DOI 10.1016/S0742-8413(98)10106-8
Open Access Status Not yet assessed
Volume 122
Issue 2
Start page 197
End page 204
Total pages 8
Place of publication Philadelphia, PA, United States
Publisher Elsevier
Language eng
Subject 2403 Immunology
3004 Pharmacology
Abstract Nifedipine oxidase and diazepam C-hydroxylase were tested as activities for selectively measuring CYP3A enzymes using liver microsomes from male and female human organ donors, male and female Wistar rats and male and female estuarine crocodiles. The association between CYP3A enzymes and these monooxygenations was confirmed for the human samples. Male rat samples had lower specific contents of CYP3A apoprotein than the human samples but had equivalent (nifedipine) or higher (diazepam) monooxygenase specific activities. CYP3A apoprotein was undetectable in female rat samples which had very low activities towards both substrates. Enzyme inhibition studies showed that diazepam C-hydroxylase of male rat liver was attributable to CYP3A but corresponding results for female rats suggested a contribution from non-CYP3A enzyme. Western blotting with immunochemical detection using anti-CYP3A4 IgG suggested the presence of putative CYP3A apoprotein in male and female crocodile liver samples and inhibition studies with diazepam as substrate suggested the presence of CYP3A subfamily monooxygenase activity in these enzyme preparations. Results for nifedipine oxidase with male and female rat liver and male crocodile liver suggested major contributions to catalysis from non-CYP3A enzymes. Inhibition studies suggested that a higher proportion of nifedipine oxidase in female crocodile liver may be attributable to the putative CYP3A enzyme(s) than in male crocodile liver. These results show the need for care in the assessment of CYP3A activity of fractionated tissues when using these substrates in cross-species studies and where gender is a variable. Copyright (C) 1999 Elsevier Science Inc.
Keyword CYP3A
Diazepam
Estuarine crocodile
Human
Immunochemical inhibition
Irreversible inactivation
Monooxygenase
Nifedipine
Rat
Triacetyloleandomycin
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Chemistry and Molecular Biosciences
 
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Created: Wed, 13 Sep 2017, 11:18:34 EST by Dr Steven Mason on behalf of School of Chemistry & Molecular Biosciences