Cimetidine: An inhibitor and an inducer of rat liver microsomal cytochrome p-450

Wright A.W.E., Winzor D.J. and Reilly P.E.B. (1991) Cimetidine: An inhibitor and an inducer of rat liver microsomal cytochrome p-450. Xenobiotica, 21 2: 193-203. doi:10.3109/00498259109039461


Author Wright A.W.E.
Winzor D.J.
Reilly P.E.B.
Title Cimetidine: An inhibitor and an inducer of rat liver microsomal cytochrome p-450
Journal name Xenobiotica   Check publisher's open access policy
ISSN 0049-8254
Publication date 1991-01-01
Sub-type Article (original research)
DOI 10.3109/00498259109039461
Volume 21
Issue 2
Start page 193
End page 203
Total pages 11
Publisher Informa Healthcare
Subject 3004 Pharmacology
3005 Toxicology
1303 Specialist Studies in Education
2307 Health, Toxicology and Mutagenesis
1300 Biochemistry, Genetics and Molecular Biology
Abstract 1. Cimetidine pretreatment of male Sprague-Dawley rats caused a significant increase in the specific content of total hepatic cytochrome P-450, supporting the hypothesis that this H2-receptor antagonist has monooxygenase induction effects. 2. Quantitative ultrastructural studies of liver of cimetidine-pretreated animals also supported this hypothesis in showing a significant proliferation of smooth endoplasmic reticulum. These ultrastructural changes were qualitatively similar to those produced by treatment of rats with phenobarbital, a well-characterized monooxygenase-inducing agent whose effects were studied for comparative purposes. 3. Competitive inhibition of metoprolol αhydroxylation by cimetidine in liver microsomes prepared from untreated animals (Ki = 18.8 μM) was also demonstrated. 4. These results allowed testing of the hypothesis (Burnet el al. 1986) that inhibition of a defined monooxygenase should lead to induction of the synthesis of the relevant cytochrome P-450 isozyme. 5. The finding that metoprolol αhydroxylase activity of liver microsomes was lowered, not elevated, by pretreatment of animals with cimetidine argues against the concept of a causal link between monooxygenase inhibition and induction.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: Scopus Import - Archived
 
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