Effect of endotoxic shock on kinetics of system A amino acid transport in rat soleus muscle

Abstract

This study evaluated the kinetics of system A amino acid transport in soleus muscle during endotoxic shock. Fasted male rats (80-100 g) were killed by decapitation 5 h after the intravenous injection of saline (control) or 20 mg/kg Salmonella enteritidis endotoxin. Soleus muscles (40 mg) from control or endotoxic rats were incubated in oxygenated Krebs-Ringer-bicarbonate buffer (pH 7.4) at 37 degrees C for 20, 40, or 60 min. Initial rates of entry of alpha-aminoisobutyric acid (AIB) into the inulin-inaccessible space of muscles were measured over a wide range of AIB concentrations (0.1-20.0 mM). Initial rates of AIB transport were separated into two parallel transport processes, a saturable carrier-mediated component and a nonsaturable passive diffusive process. The diffusion constant for the nonsaturable process in the endotoxic muscles (0.36 h-1) was 38% greater than control muscles (0.26 h-1). The maximum rate of AIB transport decreased from 55.6 +/- 3.3 nmol . g dry wt-1 . min-1 in controls to 18.3 +/- 1.9 nmol . g dry wt-1 . min-1 in endotoxic muscles. The apparent Km for saturable AIB transport was not different between control (1.68 +/- 0.12 mM) and endotoxic muscles (1.64 +/- 0.19 mM). Alterations of system A amino acid transport in endotoxic soleus muscles were due to an increase in passive AIB diffusion and a decrease in the number and/or activity of existing carriers and not to a change in carrier affinity for AIB. These results elucidate the mechanism for the decreased amino acid transport (system A) by soleus muscle in endotoxic shock.