Effects of Anaesthetics on Protein Synthesis in Isolated Rat Hepatocytes: Inhibition by Diethyl Ether in Contrast to No Influence by Pentobarbital and Fentanyl

Abstract

Hepatocytes were isolated from livers of fasted rats by a two-step Ca+ +-free/collagenase perfusion method. Suspensions of parenchymal liver cells were incubated in the absence and presence of three different anaesthetics, diethyl ether, pentobarbital and fentapyl at various concentrations. Their influence on the hepatocytes was monitored by measuring protein synthesis as the incorporation of L-(UJ4C) valine (50 mCi/ mol, 4.2 mM) into liver proteins. Diethyl ether representing anaesthetics mainly affecting cellular membranes unspecifically, inhibited protein synthesis markedly, concentrations of approximately 10, 20 and 30 mM caused 27, 50 and 74 per cent inhibition respectively, of cellular protein synthesis. The rate of synthesis of medium proteins was somewhat more reduced indicating a greater susceptibility of the synthetic process of these proteins or that ether also inhibited protein secretion from cells to media. The effect of diethyl ether was completely reversible when the anaesthetic was removed by changing the medium. Pentobarbital representing barbiturate anaesthetics, reduced the synthesis of cell and medium proteins very little, while the opiate anaesthetic fentanyl had no inhibitory effect. These results demonstrate a potential hepatotoxic mechanism for membrane active drugs like diethyl ether. They also indicate that special precautions should be taken when this type of anaesthesia is used during the study of hepatic protein synthesis.