Picrotoxin is a CYP1A1 inducer in rainbow trout hepatocytes.
Picrotoxin is a CYP2B inducer in mammals (1). However, in primary cultures of rainbow trout hepatocytes we showed CYP1A1 gene expression to be strongly induced as characterized by 7-ethoxyresorufin-O-deethylase activity, immunoblots of CYP1A1 protein, and Northern blots of CYP1A1 mRNA. Induction of CYP1A1 in these cells appeared to be via the aromatic hydrocarbon (Ah) receptor as indicated by increased levels of Ah receptor in the nuclear extracts of picrotoxin-treated cells. Picrotoxin induction of CYP1A1 was blocked by actinomycin D. Superinduction of CYP1A1 mRNA occurred in cells treated with cycloheximide. Co-incubation of hepatocytes with picrotoxin and a saturating concentration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) resulted in synergistic increases in CYP1A1 gene expression. These results suggest that picrotoxin induction of CYP1A1 is regulated at the level of transcription and may involve an alternative mechanism(s) to that of TCDD.
Sadar
M D
MD
Department of Zoophysiology, University of Göteborg, Sweden.
Ash
R
R
Andersson
T B
TB
D000818:Animals; D015152:Blotting, Northern; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D017686:Oncorhynchus mykiss; D010088:Oxidoreductases / Q000096:biosynthesis*; D010852:Picrotoxin / Q000494:pharmacology*; D018336:Receptors, Aryl Hydrocarbon / Q000096:biosynthesis
D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D010852:Picrotoxin; D018336:Receptors, Aryl Hydrocarbon