7-Ethoxycoumarin and 7-ethoxyresorufin O-deethylase in human foetal and adult liver: studies with monoclonal antibodies.
The 7-ethoxycoumarin and 7-ethoxyresorufin O-deethylase activities were investigated in the microsomal fractions from 5 human adult and 3 foetal livers and 5 human foetal adrenals. The enzyme activity expressed as pmol/min. per mg microsomal protein was higher with 7-ethoxyresorufin as substrate in all investigated specimens with average values (+/- S.E.M.) of 74 +/- 27, 13 +/- 3 and 12 +/- 1 in adult and foetal livers and foetal adrenals, respectively. Monoclonal antibodies raised against 3-methylchloranthrene or phenobarbital induced rat liver cytochrome P-450 were investigated with respect to their inhibiting effects on the rate of O-deethylation of both substrates in human adult liver. Only the monoclonal antibody against the 3-methylcholanthrene induced cytochrome P-450 inhibited the O-deethylation of 7-ethoxyresorufin to 64 to 79 percent of control values. The other antibody had no effect on this or the other O-deethylase activity. Thus, the 7-ethoxyresorufin O-deethylase is partly catalyzed in human adult liver by a cytochrome with an epitope that is recognized by the monoclonal antibody against 3-methylcholanthrene induced rat liver cytochrome P-450. With foetal liver the low activity of the enzyme became unmeasurable in the presence of this antibody.
Pacifici
G M
GM
Division of Clinical Pharmacology, University Hospital, Uppsala, Sweden.
Park
S S
SS
Gelboin
H V
HV
Rane
A
A
D015660:7-Alkoxycoumarin O-Dealkylase; D000311:Adrenal Glands / Q000196:embryology / Q000201:enzymology; D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006801:Humans; D008099:Liver / Q000196:embryology / Q000201:enzymology; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D008875:Middle Aged; D010088:Oxidoreductases / Q000378:metabolism*; D010105:Oxygenases / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D013997:Time Factors
D000911:Antibodies, Monoclonal; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D010105:Oxygenases; D015660:7-Alkoxycoumarin O-Dealkylase; D019363:Cytochrome P-450 CYP1A1