PMID- 8212741
OWN - NLM
STAT- MEDLINE
DCOM- 19931028
LR  - 20190909
IS  - 0049-8254 (Print)
IS  - 0049-8254 (Linking)
VI  - 23
IP  - 6
DP  - 1993 Jun
TI  - Effect of phenobarbital and other model inducers on cytochrome P450 isoenzymes in 
      primary culture of dog hepatocytes.
PG  - 681-92
AB  - 1. The effects of phenobarbital (PB), beta-naphthoflavone (beta-NF), omeprazole 
      (Omep) and rifampicin (Rif) on drug-metabolizing activities in dog hepatocytes, 
      cultured with William's medium E, were examined. 2. The drug metabolizing 
      activities of the hepatocytes decreased during culture; 7-ethoxycoumarin 
      O-deethylase (ECOD) activity was nearly 70% of initial value at 72 h, but 
      7-methoxycoumarin O-demethylase (MCOD), 7-propoxycoumarin O-depropylase (PCOD), 
      progesterone 6 beta-hydroxylase (6 beta-OH-P), progesterone 16 alpha-hydroxylase 
      (16 alpha-OH-P), progesterone 21-hydroxylase (21-OH-P), 7-ethoxyresorufin 
      O-deethylase (EROD) activities and total cytochrome P450 content were approx. 
      50%. 3. When the hepatocytes were cultured with PB, the enzyme activities 
      increased time- and dose-dependently. MCOD, ECOD and PCOD activities increased 
      5-8 fold with 2 mM PB in 96 h. Similar results were obtained for 6 beta-OH-P, 16 
      alpha-OH-P and 21-OH-P activities, and total cytochrome P450. The effect of PB 
      was abolished when 2.5 microM cycloheximide or 0.1 microM actinomycin D was 
      included in the culture. 4. Treatment of hepatocytes with 40 microM beta-NF for 
      72 h resulted in 25-fold elevation of EROD activity. beta-NF enhanced PCOD 
      activity approx. six-fold, while ECOD increased only slightly, and 7-MCOD 
      negligibly. 5. Omep (100 microM) increased EROD activity nearly 10-fold, and 25 
      microM Rif increased 6 beta-OH-P activity approx. 8-fold, but ECOD only slightly. 
      6. Western blot analysis of microsomes from cultured dog hepatocytes with 
      anti-rat CYP 2B1 antibodies indicated that PB increased an 
      immunochemically-reactive protein. The protein showed the same mobility as the 
      major dog P450 isozyme (cytochrome P450 PBD-2 or CYP 2B11) purified from liver 
      microsomes of PB-treated male beagle dog. In a similar manner, induction of 
      cytochrome P450 PBD-1 (CYP 3A12) by PB was confirmed.
FAU - Nishibe, Y
AU  - Nishibe Y
AD  - Shionogi Research Laboratories, Shionogi and Co., Ltd., Osaka, Japan.
FAU - Hirata, M
AU  - Hirata M
LA  - eng
PT  - Journal Article
PL  - England
TA  - Xenobiotica
JT  - Xenobiotica; the fate of foreign compounds in biological systems
JID - 1306665
RN  - 0 (Benzoflavones)
RN  - 0 (Isoenzymes)
RN  - 6051-87-2 (beta-Naphthoflavone)
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
RN  - EC 1.- (Oxidoreductases)
RN  - EC 1.14.13.- (7-Alkoxycoumarin O-Dealkylase)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A1)
RN  - EC 1.14.14.1 (Steroid 16-alpha-Hydroxylase)
RN  - KG60484QX9 (Omeprazole)
RN  - VJT6J7R4TR (Rifampin)
RN  - YQE403BP4D (Phenobarbital)
SB  - IM
MH  - 7-Alkoxycoumarin O-Dealkylase/metabolism
MH  - Animals
MH  - Benzoflavones/pharmacology
MH  - Blotting, Western
MH  - Cells, Cultured
MH  - Cytochrome P-450 CYP1A1
MH  - Cytochrome P-450 Enzyme System/*metabolism
MH  - Dogs
MH  - Enzyme Induction/drug effects
MH  - Isoenzymes/*metabolism
MH  - Kinetics
MH  - Liver/drug effects/*enzymology
MH  - Male
MH  - Microsomes, Liver/drug effects/enzymology
MH  - Omeprazole/pharmacology
MH  - Oxidoreductases/metabolism
MH  - Phenobarbital/*pharmacology
MH  - Rifampin/pharmacology
MH  - Steroid 16-alpha-Hydroxylase
MH  - beta-Naphthoflavone
EDAT- 1993/06/01 00:00
MHDA- 1993/06/01 00:01
CRDT- 1993/06/01 00:00
PHST- 1993/06/01 00:00 [pubmed]
PHST- 1993/06/01 00:01 [medline]
PHST- 1993/06/01 00:00 [entrez]
AID - 10.3109/00498259309059405 [doi]
PST - ppublish
SO  - Xenobiotica. 1993 Jun;23(6):681-92. doi: 10.3109/00498259309059405.