TRANSPORT OF L-GLUTAMINE AND L-GLUTAMATE ACROSS SINUSOIDAL MEMBRANES OF RAT-LIVER - EFFECTS OF STARVATION, DIABETES AND CORTICOSTEROID TREATMENT

There is increasing evidence that membrane transporters for glutamine and glutamate are involved in control of liver metabolism in health and disease. We therefore investigated the effects of three catabolic states [starvation (60 h). diabetes (4 days after streptozotocin treatment) and corticosteroid (8-day dexamethasone) treatment] associated with altered hepatic amino acid metabolism on the activity of glutamine and glutamate transporters in sinusoidal membrane vesicles, from livers of treated rats. In control preparations. L-[C-14]glutamine uptake was largely Na+-dependent. but L-[C-14]glutamate uptake was largely Na+-independent. V(max) values for Na+-dependent uptake of glutamine and/or glutamate exceeded control values (by about 2- and 12-fold respectively) in liver membrane vesicles from starved (glutamine), diabetic (glutamate) or steroid-treated (glutamine and glutamate) rats. The K(m) values for Na+-dependent transport of glutamine or glutamate and the rates of their Na+-independent uptake were not significantly altered by any treatment. Na+-independent glutamate uptake appeared to include a dicarboxylate-exchange component. The patterns of inhibition of glutamine and glutamate uptake by other amino acids indicated that the apparent induction of Na+-dependent amino acid transport in catabolic states included increased functional expression of systems A, N (both for glutamine) and X(ag)-(for glutamate). The results demonstrate that conditions resulting in increased secretion of catabolic hormones (e.g. coricosteroid, glucagon) are associated with increased capacity for Na+-dependent transport of amino acids into liver cells from the blood. The modulation of hepatic permeability to glutamine and glutamate in these situations may control the availability of amino acids for intrahepatic metabolic processes such as ureagenesis, ammonia detoxification and gluconeogenesis.