Molecular Pharmacology, Vol 4, 465-470, Copyright © 1968 by the American Society for Pharmacology and Experimental Therapeutics

Inhibition of Tryptophan Pyrrolase Induction by Carbon Tetrachloride in Rats

¹ Department of Pharmacology, University of Iowa College of Medicine, Iowa City, Iowa 62240

The inducing action of hydrocortisone and L-tryptophan on hepatic tryptophan pyrrolase in rats treated previously with CCl₄ was studied. CCl₄ exhibited a dose-dependent (and time-dependent) inhibitory action on the hematin-activated (apoenzyme) form of tryptophan pyrrolase but had no effect on basal holoenzyme activity. A low dose of CCl₄ (0.1 ml/kg) abolished induction of the holoenzyme by hydrocortisone but had little effect on the tryptophan-induced holoenzyme or total enzyme activity. This inhibitory action of CCl₄ required between 6 and 12 hr of exposure of the animal to CCl₄ in vivo, i.e., prior to administration of the inducing agents. A 10-fold increase in CCl₄ dose to 1.0 ml/kg did not abolish the inducing action of tryptophan; however, the enzyme response to tryptophan administration was appreciably reduced in rats receiving the higher CCl₄ dose.

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ACKNOWLEDGMENT This investigation was supported by Grants GM12675 and 5-T01-GM 01308 from the National Institute of General Medical Sciences.