Liver microsomal drug-metabolizing enzyme activity: enhancement by blockade of degradative processes in promethazine-treated rats.
Daily injection of promethazine over 4 days significantly increased the liver cytochrome P-450 content and ethyl morphine N-demethylase activity. These increases were evident after the first dose and were prevented by puromycin or actinomycin D administration. Repeated administration of promethazine does not increase the liver's ability to incorporate [14]C DL-leucine in microsomes but slows down the decay of radioactivity in microsomes previously labelled with ([14C]-guanidino) arginine. Repeated treatment with promethazine leads to a marked proliferation of the rough endoplasmic reticulum (RER) and a slight increase in the smooth endoplasmic reticulum (SER). Our findings suggest that the enhancement of P-450 and EM-ase activity result from the decelerating effect of promethazine on protein degradation.
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D005037:Ethylmorphine-N-Demethylase / Q000378:metabolism; D008099:Liver / Q000648:ultrastructure; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D011398:Promethazine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011691:Puromycin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D003609:Dactinomycin; D011691:Puromycin; D003577:Cytochrome P-450 Enzyme System; D005037:Ethylmorphine-N-Demethylase; D011398:Promethazine