Na(+)-dependent glutamine transport in the liver of tumour-bearing rats

Abstract

In rats with advanced malignant disease, the liver extracted circulating glutamine at a ratio three times faster than the liver of control non-tumour-bearing animals. This augmented uptake occurred in spite of a fall in circulating glutamine levels, implying an increase in hepatocyte plasma membrane transport. Na(+)-dependent glutamine transport activity (System N) was increased nearly two-fold in hepatocyte plasma membrane vesicles from tumour-bearing rats; this increase in System N activity was proportional to tumour size and was due to an increase in carrier Vmax with no change in carrier affinity. Measurement of System N activity in isolated hepatocytes incubated with serum from tumour-bearing rats demonstrated a significant increase in glutamine transport compared with cells incubated with serum from control rats. These data indicate that the liver of rats with advanced malignant disease displays accelerated glutamine consumption. This increased uptake is due, in part, to enhanced carrier-mediated transport activity, and is mediated by a circulating factor(s) that is not present (or inactive) in non-tumour-bearing controls.