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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1989-4-21
pubmed:abstractText
Drug metabolic capacity in liver microsomes of 14 rat inbred strains was investigated. Cytochrome P-450 content as well as the following enzyme activities were measured: NADPH cyt. c(P-450) reductase (Red.), aminopyrine N-demethylase (APDM), ethoxycoumarin O-deethylase (ECOD), 1-naphthol: UDP-glucuronosyltransferase (NGT) and hydrolysis of acetylsalicylic acid (ASA; measured at pH 5.5 and pH 7.4). All enzymes measured were found to exhibit statistically significant inter-strain differences. In males the enzyme activities varied over a 7.3-fold (ECOD) to 1.4-fold (cytochrome P-450) range. Other inter-strain differences were generally larger than 2-fold: ASA-hydrolysis at pH 5.5 and 7.4 (3.9- and 3.3-fold variation, respectively), NGT and Red. (2.1-fold variation) and APDM (1.8-fold variation). In females similar, but somewhat smaller inter-strain differences were observed. Correlations between different enzyme activities were generally poor (correlation coefficients r less than 0.7). An exception was the correlation between ASA-hydrolysis at pH 5.5 and pH 7.4 (r = 0.79). We conclude that ASA hydrolysis at pH 5.5 and 7.4 is mediated by the same enzyme or by coregulated enzymes and that all other activities are mediated by different or differentially regulated enzymes. Based on analysis of variance and subsequent inter-strain comparisons, all strains appear to express a unique profile of liver microsomal drug metabolism. No two strains are identical with respect to all activities measured. We suggest that differences between inbred rat strains and particularly the difference in balance between different enzymes in various strains can be used advantageously in pharmacological and toxicological experiments.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
38
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
759-65
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1989
pubmed:articleTitle
Comparison of microsomal drug-metabolizing enzymes in 14 rat inbred strains.
pubmed:affiliation
Department of Pharmacology, Faculty of Pharmacy, University of Utrecht, The Netherlands.
pubmed:publicationType
Journal Article, Comparative Study