Molecular Pharmacology, Vol 15, 154-164, Copyright © 1979 by the American Society for Pharmacology and Experimental Therapeutics

Immunological Comparison of Hepatic and Extrahepatic Cytochromes P-450

¹ Department of Biochemistry and Center in Environmental Toxicology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232

Antibodies were raised to two apparently homogeneous cytochromes P-450 prepared from liver microsomes of phenobarbital- and 3-methylcholanthrene-treated rats; microsomal fractions were prepared from the livers, lungs, kidneys, testes, spleens, hearts, small intestines, colons, stomachs, and brains of untreated and phenobarbital- and 3-methylcholanthrene-treated rats. Cross reactivity was observed in each tissue with at least one of the two antibodies as judged by immunodiffusion analysis. Inhibition of benzo(a)pyrene hydroxylase or 7-ethoxycoumarin O-deethylase activity was observed with microsomes prepared from each tissue with the exception of spleen and colon; inhibition curves were dependent upon the substrate and antibody used as well as the pretreatment of the animals from which the microsomes were prepared. As a general rule, microsomes prepared from 3-methylcholanthrene-treated rats were inhibited most readily by antibody raised to cytochrome P-450 isolated from liver microsomes prepared from 3-methylcholanthrene-treated rats, and the same general rule held for phenobarbital induction; however, several exceptions were noted. On the basis of these results, the microsomal P-450s of extrahepatic tissues are, in general, immunologically similar to the major hepatic microsomal P-450s in the rat.

Note:
ACKNOWLEDGMENTS We are thankful to Drs. R. A. Neal, F. Chytil, and D. E. Ong for the use of their fluorimeters.

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