Molecular Pharmacology, Vol 6, 231-239, Copyright © 1970 by the American Society for Pharmacology and Experimental Therapeutics

The Effect of 3-Amino-1,2,4-triazole on the Phenobarbital-Induced Formation of Hepatic Microsomal Membranes

¹ Departments of Pathology and Medicine, Mount Sinai School of Medicine of The City University of New York, New York, New York 10029

3-Amino-1,2,4-triazole was administered to rats in combination with phenobarbital. The hepatic endoplasmic reticulum was studied chemically and by electron microscopy. The increases in cytochrome P-450 and drug hydroxylase activity produced by phenobarbital alone were partially counteracted by administration of aminotriazole together with phenobarbital. The increases in membranes of the endoplasmic reticulum, observed by electron microscopy and measured by microsomal phospholipid, were comparable in animals receiving phenobarbital alone and in combination with aminotriazole. Aminotriazole treatment alone does not produce proliferation of endoplasmic reticular membranes. In the presence of an inducer such as phenobarbital, interference with cytochrome P-450 biosynthesis by aminotriazole does not affect ineduction of the formation of membranes of the hepatic endoplasmic reticulum. These results suggest that induced increases of cytochrome P-450 and of the membranes of endoplasmic reticulum may be controlled by separate mechanisms.

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ACKNOWLEDGMENTS The authors wish to thank Dr. J. Baron and Dr. T. R. Tephly for their technical advice. The authors acknowledge the expert technical assistance of Mrs. Lydia Castellar.