Ontogenic development of 7-ethoxycoumarin and 7-ethoxyresorufin O-deethylase in the rat and effect of monoclonal antibodies.
The O-deethylase activities with 7-ethoxycoumarin (ECDE) and 7-ethoxyresorufin (ERDE) as substrates were investigated in the liver microsomal fraction of newborn, 1 week, 2 weeks, 1 month and 2 months old rats. The rates of O-deethylation of both substrates were lowest in newborn rats at which stage the specific activities (pmol x min.-1 x mg-1 protein; mean +/- S.D.) of ECDE and ERDE were 19.0 +/- 0.2 and 6.0 +/- 0.5, respectively. In 1 week old animals, the rate of ECDE had reached the highest values (270 +/- 81 pmol x min.-1 x mg-1 protein). Thereafter, it decreased to a minimum (70.9 +/- 14.8 pmolmin.-1 x mg-1 protein) at 2 months of age. The rate of ERDE reached the highest activity (129 +/- 7.1 pmol x min.-1 x mg-1 protein) in 1 month old animals. The effects monoclonal of antibodies (MAb), on ECDE and ERDE were studied. The MAb were raised against 3-methylcholanthrene (MAb 1-7-1) or phenobarbital (MAB 2-66-3) induced rat liver microsomal cytochrome P-450. Only the former antibodies were inhibitory to the O-deethylation of 7-ethoxyresorufin. This reaction was inhibited to a similar extent (by 31-33%) in rat liver microsomes from 1 week and 2 months old animals. None of the antibodies exerted any effect on the O-deethylation of 7-ethoxycoumarin.
Pacifici
G M
GM
Division of Clinical Pharmacology, University Hospital, Uppsala, Sweden.
Park
S S
SS
Gelboin
H W
HW
Rane
A
A
D015660:7-Alkoxycoumarin O-Dealkylase; D000375:Aging / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005260:Female; D008099:Liver / Q000201:enzymology; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D008862:Microsomes, Liver / Q000201:enzymology; D010088:Oxidoreductases / Q000378:metabolism*; D010105:Oxygenases / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D000911:Antibodies, Monoclonal; D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D010105:Oxygenases; D015660:7-Alkoxycoumarin O-Dealkylase; D019363:Cytochrome P-450 CYP1A1; D010634:Phenobarbital