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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
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pubmed:dateCreated |
1977-6-30
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pubmed:abstractText |
Primary monolayer culture of adult rat hepatocytes represents a novel and potentially useful technique to study many aspects of hepatic physiology for extended periods of time in vitro (J Cell Biol 59:722-734, 1973). In examining the hepatic drug-metabolizing system in these cells, we have discovered that the conditions of cell culture exert rapid, selective, and reproducible changes in microsomal enzymes. In the 24- to 48-hr period immediately following preparation and culture of the isolated parenchymal cells, the level of the drug-binding microsomal hemoprotein, cytochrome P-450, measured in extracts of cell homogenates, declined to less than 20% of its in vivo level, whereas NADPH-cytochrome c reductase activity was only moderately reduced and glucose-6-phosphatase activity remained unchanged. The activity of aminopyrine-N-demethylase and aniline hydroxylase also fell, paralleling the level of cytochrome P-450. By contrast, p-nitroanisole O-demethylase activity was unchanged in the cultured hepatocytes despite evidence (type I binding spectrum, NADPH requirement, inhibition by carbon monoxide or by SKF 525A) that p-nitroanisole O-demethylase is a cytochrome P-450-dependent enzyme. In culture, as in vivo, aromatic polycyclic hydrocarbons stimulated p-nitroanisole O-demethylase and aryl hydrocarbon (benzo [a] pyrene) hydroxylase activities; however, this effect was unaccompanied by a detectable increase in total carbon monoxide-binding hemoprotein. The data indicate that the profile of microsomal oxidase enzymes and their control undergo striking changes as hepatocytes adapt to cell culture.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Aminopyrine N-Demethylase,
http://linkedlifedata.com/resource/pubmed/chemical/Aniline Hydroxylase,
http://linkedlifedata.com/resource/pubmed/chemical/Aryl Hydrocarbon Hydroxylases,
http://linkedlifedata.com/resource/pubmed/chemical/Benzopyrenes,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome P-450 Enzyme System,
http://linkedlifedata.com/resource/pubmed/chemical/NADPH-Ferrihemoprotein Reductase,
http://linkedlifedata.com/resource/pubmed/chemical/Nitroanisole O-Demethylase,
http://linkedlifedata.com/resource/pubmed/chemical/Pharmaceutical Preparations
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0016-5085
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
72
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1232-9
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pubmed:dateRevised |
2009-10-27
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pubmed:meshHeading |
pubmed-meshheading:404208-Aminopyrine N-Demethylase,
pubmed-meshheading:404208-Aniline Hydroxylase,
pubmed-meshheading:404208-Animals,
pubmed-meshheading:404208-Aryl Hydrocarbon Hydroxylases,
pubmed-meshheading:404208-Benzopyrenes,
pubmed-meshheading:404208-Cells, Cultured,
pubmed-meshheading:404208-Cytochrome P-450 Enzyme System,
pubmed-meshheading:404208-Enzyme Induction,
pubmed-meshheading:404208-Liver,
pubmed-meshheading:404208-Metabolic Detoxication, Drug,
pubmed-meshheading:404208-Microsomes, Liver,
pubmed-meshheading:404208-NADPH-Ferrihemoprotein Reductase,
pubmed-meshheading:404208-Nitroanisole O-Demethylase,
pubmed-meshheading:404208-Pharmaceutical Preparations,
pubmed-meshheading:404208-Rats
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pubmed:year |
1977
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pubmed:articleTitle |
Drug metabolism in adult rat hepatocytes in primary monolayer culture.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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