Immunochemical similarity of P-450 HFLa, a form of cytochrome P-450 in human fetal livers, to a form of rat liver cytochrome P-450 inducible by macrolide antibiotics.
A protein immunochemically related to P-450 HFLa, a form of cytochrome P-450 purified from human fetal livers, was detected in rat liver microsomes. The content of the immunoreactive protein in rat liver microsomes was increased by treatments with phenobarbital, pregnenolone 16 alpha-carbonitrile (PCN), erythromycin, erythromycin estolate, and oleandomycin but not with 3-methylcholanthrene, imidazole, ethanol, isosafrole, josamycin, midecamycin, or miocamycin. The activity of erythromycin N-demethylase correlated with the content of the immunoreactive protein in rat liver microsomes (r = 0.72). In addition, anti-P-450 HFLa IgG inhibited erythromycin N-demethylase in liver microsomes from erythromycin- or oleandomycin-pretreated rats. Furthermore, the content of the immunoreactive protein highly correlated with that of P-450 PB-1, which is distinct from Waxman's terminology, and is one of the forms of PCN-inducible cytochrome P-450s (r = 0.95). From these results and the results reported so far, it seems possible that P-450 HFLa is one of the forms of cytochrome P-450 inducible by glucocorticoids.
Kitada
M
M
Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Igoshi
N
N
Kamataki
T
T
Itahashi
K
K
Imaoka
S
S
Komori
M
M
Funae
Y
Y
Rikihisa
T
T
Kanakubo
Y
Y
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis* / Q000096:biosynthesis / Q000276:immunology; D004591:Electrophoresis, Polyacrylamide Gel; D004790:Enzyme Induction / Q000187:drug effects; D004917:Erythromycin / Q000494:pharmacology*; D005333:Fetus; D006801:Humans; D007118:Immunoassay; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D009827:Oleandomycin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D004917:Erythromycin; D003577:Cytochrome P-450 Enzyme System; D009827:Oleandomycin