Abstract
The effect of various foreign compounds, given to rats, on the activity of hepatic microsomal enzymes has been studied. Carbon tetrachloride, coumarin, ethionine, and thioacetamide brought about an impairment of phosphatases (substrates: glucose 6-phosphate, inorganic pyrophosphate, inosine diphosphate, guanosine diphosphate, or uridine diphosphate) and slight reduction of drug-metabolizing enzymes (hexobarbital oxidase, butylated hydroxytoluene oxidase, coumarin 3-hydroxylase, nitroanisole demethylase, or codeine demethylase). Hexobarbital, phenobarbital, 3-methylcholanthrene, 4-methylcoumarin, butylated hydroxytoluene (BHT), BHT-alcohol and BHT-alcohol- O-methyl ether had no effect on phosphatases but induced the synthesis of drug-metabolizing enzymes. Antagonism was found between coumarin and 4-methylcoumarin, carbon tetrachloride and 3-methylcholanthrene or phenobarbital in their effect on microsomal enzymes when pairs of these compounds were administered simultaneously, indicating a common site in their action on the endoplasmic reticulum.
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