Influence of medium composition on 7-alkoxycoumarin O-dealkylase activities of rat hepatocytes in primary maintenance culture.
1. The activities of 7-methoxycoumarin (7-MCOD), 7-ethoxycoumarin (7-ECOD) and 7-propoxycoumarin (7-PCOD) O-dealkylases decreased by 75-90% during culture of rat hepatocytes for 72 h. 2. The addition of dexamethasone (D) produced a stabilization or modest enhancement of 7-ECOD and 7-PCOD activities depending on the medium used; D was without effect on 7-MCOD activity. 3. The addition of nicotinamide (N) produced some stabilization of 7-ECOD and 7-PCOD activities but not of 7-MCOD activity. 4. The addition of D + N was associated with large increases in 7-ECOD and 7-PCOD activities, again with little effect on 7-MCOD activity. 5. Ethoxyresorufin O-dealkylase activity correlated with 7-ECOD/7-PCOD activities, whereas pentoxyresorufin O-dealkylase activity correlated with 7-MCOD activity. 6. It is concluded that D exerts a selective effect on certain forms of cytochrome P-450, but that more than one mechanism is probably implicated in this effect. 7. The magnitudes of induction of 7-ECOD activity by phenobarbitone and beta-naphthoflavone were blunted when cells were treated in culture when compared to treatment in vivo; the presence of D in the culture medium did not modify this phenomenon.
Warren
M
M
Department of Physiology and Pharmacology, Medical School, Queen's Medical Centre, Nottingham, U.K.
Fry
J R
JR
D015660:7-Alkoxycoumarin O-Dealkylase; D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology; D002478:Cells, Cultured; D003470:Culture Media; D003907:Dexamethasone / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009536:Niacinamide / Q000494:pharmacology; D010105:Oxygenases / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014468:Umbelliferones / Q000378:metabolism; D019324:beta-Naphthoflavone
D001571:Benzoflavones; D003470:Culture Media; D014468:Umbelliferones; D009536:Niacinamide; C007929:herniarin; D019324:beta-Naphthoflavone; D003907:Dexamethasone; D010105:Oxygenases; D015660:7-Alkoxycoumarin O-Dealkylase; D010634:Phenobarbital