System ASC and sodium-independent neutral amino acid transport in muscle of uremic rats

Abstract

Neutral amino acids are transported by systems A, ASC, and L. In the previous companion study we demonstrated that 2-(methylamino) isobutyrate (MeAIB) is a specific substrate for system A in muscle and that stimulation of system A by physiological concentrations of insulin is preserved in acute uremia (ARF). Insulin-stimulated uptake of the nonspecific probes cycloleucine and alpha-aminoisobutyrate (AIB) is reportedly blunted by uremia; the cause of this and whether transport by systems ASC and L is defective are unknown. In this study we examined these questions using incubated epitrochlearis muscles from normal fed, ARF, and sham-operated control (SO) rats. System ASC was studied by measuring AIB and cycloleucine uptake in the presence of inhibitors of systems A and L, MeAIB and 2-amino-2-norbornane carboxylic acid (BCH), respectively. System L was defined as sodium-independent uptake suppressible by BCH. Excess MeAIB completely inhibited insulin-stimulated AIB and cycloleucine uptake, indicating that system A is the only insulin-responsive neutral amino acid carrier in muscle. In ARF and SO mucles both AIB and cycloleucine uptake were indistinguishable in the absence or presence of insulin. Moreover, ARF caused no detectable abnormality in transport by systems ASC and L.