Control of hepatic proteolysis by amino acids. The role of cell volume

Abstract

1. Proteolysis in isolated perfused rat liver was monitored as [3H]leucine release into effluent perfusate after in vivo labeling by intraperitoneal injection of [3H]leucine about 16 h prior to the perfusion experiment. Exposure of the livers to hypotonic perfusion media (175-295 mOsmol.l-1) increased liver mass due to cell swelling and inhibited [3H]leucine release. The extent of inhibition of [3H]leucine release was linearly related to the liver-mass increase, regardless of whether livers from fed or 24-h-starved rats were studied. 2. Infusion of glycine (0.5-3 mmol.l-1) or glutamine (0.5-3 mmol.l-1) during normotonic perfusions (305 mOsmol.l-1) led to a concentration-dependent increase of liver mass and inhibition of [3H]leucine release. The inhibition of [3H]leucine release was again strongly dependent upon the increase of liver mass, regardless of whether cell swelling was induced by glutamine or glycine in normotonic perfusions, by exposure of the liver to hypotonic media or whether amino-acid-induced cell swelling was modified by the nutritional state. The effects of glutamine and glycine on [3H]leucine release were additive to the same extent as that found when the liver-mass increase was observed. 3. Alanine, serine and proline inhibited [3H]leucine release in parallel to the extent of amino-acid-induced liver-mass increase; however, the inhibition of [3H]leucine release was about twice that found when comparable degrees of cell swelling were induced either by hypotonic exposure or by addition of glutamine or glycine. The relationship between alanine-induced liver-mass increase and the inhibition of [3H]leucine release was also maintained in presence of aminooxyacetate (0.2 mmol.l-1). 4. Infusion of an amino acid mixture, roughly mimicking the concentrations found in portal venous blood, to livers from 24-h-starved or fed rats inhibited [3H]leucine release by 56.0 +/- 2.4% (n = 6) or 31.1 +/- 2.3% (n = 3), respectively, and increased liver mass by 5.0 +/- 0.1% (n = 6) or 2.2 +/- 0.3% (n = 3), respectively. Regardless of the nutritional state, there was a close relationship between the amino-acid-mixture-induced (and also phenylalanine-induced) increase of liver mass and the degree of inhibition of [3H]leucine release; however, the inhibition of [3H]leucine release was about fourfold higher than that found when comparable degrees of cell swelling were induced by hypotonic exposure.(ABSTRACT TRUNCATED AT 400 WORDS)