Effect of (—)-Emetine on Liver Microsomal Protein Synthesis in Partially Hepatectomized Rats

Abstract

1. In the early sequential response to partial hepatectomy there is an initial inhibition of liver microsomal protein-synthesizing activity in vitro comparable in duration and degree to that occurring after administration of (—)-emetine (18 μmol/kg) to intact female rats. This initial inhibition is followed by a prolonged phase of stimulated amino acid incorporating activity by liver microsomal fractions prepared from donor animals at later times.

2. There is a delayed appearance of the stimulatory phase of microsomal amino acid incorporating activity in vitro when donor animals are treated with (—)-emetine immediately after partial hepatectomy. This may be related to the finding that in these animals hepatic enzymes involved in the biosynthesis of DNA, such as deoxycytidylate deaminase and thymidine kinase, are not stimulated in the expected way.

3. By separating the two challenges and superimposing 24 h treatment with (—)-emetine on 48 h regeneration, or 24 h regeneration on 48 h (—)-emetine treatment, the liver microsomal protein-synthesizing activity can be stimulated to a greater extent than with either challenge alone. This greater stimulation occurs after the second challenge has also exerted its initial inhibitory phase response, which implies that an initial inhibitory phase may be involved in the mechanism for initiating the regenerative response.