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Journal of Pharmacology And Experimental Therapeutics, Vol. 150, Issue 3, 499-506, 1965
Copyright © 1965 by American Society for Pharmacology and Experimental Therapeutics

POTENTIATION AND INHIBITION OF agr-NAPHTHYLISOTHIOCYANATE-INDUCED HYPERBILIRUBINEMIA AND CHOLESTASIS

Robert J. Roberts 1 and Gabriel L. Plaa 1

1 Department of Pharmacology, College of Medicine, The University of Iowa, Iowa City, Iowa

It is possible to enhance the acute hyperbilirubinemic and cholestatic effects of agr- naphthylisothiocyanate (ANIT) by pretreating mice with chlorpromazine or phenobarbital. The data strongly implicate the involvement of the endoplasmic reticulum in the ANIT-induced response for the following reasons: 1) Both chlorpromazine and phenobarbital stimulate hepatic microsomes. 2) The temporal aspects of the ANIT potentiation correlate well with the stimulatory effects of chlorpromazine and phenobarbital on barbiturate metabolism. 3) The potentiation can be blocked by the simultaneous administration of ethionine or actinomycin D. 4) The time course of the diphasic effects of SKF 525-A (beta-diethylaminoethyl ethyl phenylpropylacetate HCl) on ANIT correlates well with the time course of the diphasic effect of SKF 525-A on barbiturate metabolism.

Accepted on June 25, 1965




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Characterization of ANIT-Induced Toxicity using Precision-Cut Rat and Dog Liver Slices Cultured in a Dynamic Organ Roller System
Toxicol Pathol, October 1, 2006; 34(6): 776 - 784.
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Copyright © 1965 by the American Society for Pharmacology and Experimental Therapeutics.