Molecular Pharmacology, Vol 2, 506-517, Copyright © 1966 by the American Society for Pharmacology and Experimental Therapeutics

Further Studies on the Stimulation of L-(¹⁴C)-Amino Acid Incorporation with Cycloheximide

¹ Department of Pharmacology, George Washington University School of Medicine, Washington 5, D. C.

The administration in vivo of cycloheximide increases the L-(¹⁴C)-amino acid incorporation in vitro in a rat liver microsomal system. A single injection of cycloheximide stimulates the in vitro system within the first hour. Two separate microsomal responses are recognized, which involve endogenous RNA and microsomal sensitivity to added messenger RNA, respectively. The former effect is more pronounced and prolonged; it persists for 5-6 days after a single injection of the drug, whereas the exogenous RNA effect returns to the level of the control in 2-3 days. The increased activity of the hepatic microsomal fraction isolated from cycloheximide-treated animals is not related to (a) changes in MgCl₂, requirement of the system, (b) the stabilization of the endogenous messenger RNA, (c) factors present in the supernatant fraction of the cell.

Injections of cycloheximide selectively inhibit the microsomal drug-metabolizing enzymes and prolong the hexobarbital sleeping time.

Repeated daily injections of cycloheximide slow the overall growth rate of the treated rats relative to the controls.

Note:
ACKNOWLEDGMENT This work was generously supported by Research Grants GM-13749 and CA-02978 from the U. S. Public Health Service. During the course of this work D. C. S. was the recipient of funds from Training Grant No. 5T1-GM-26 from the National Institute of General Medicine.