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.