DIETARY-REGULATION OF THE HEPATIC SYSTEM-N GLUTAMINE TRANSPORTER IN TUMOR-BEARING RATS

BACKGROUND: Hepatocytes possess a novel, plasma-membrane, sodium ion ( Na+)-independent, glutamine transporter (system n), which functions to transport glutamine out of the cell into the blood, In the tumor-bear ing rat, the activity of system n increases but its regulation is unkn own. We hypothesized that the increase in system a that occurs in rats with cancer was related to a fall in the circulating glutamine concen tration. METHODS: Tell male rats underwent flank implantation with a c ube of methylchoanthrene-induced fibrosarcoma cells and 10 rats underw ent a sh,un operation. After 9 days of standard diet, all rats were ra ndomized to receive either a glutamine-enriched oral diet or an isonit rogenous diet without supplemental glutamine, for 1 week. Tumors and l ivers were harvested 16 days postimplantation. Arterial blood samples were obtained from all animals. Hepatic plasma membrane vesicles were prepared and the carrier-mediated, Na+-independent transport of glutam ine was assayed. RESULTS: When compared to nontumor-bearing animals, t umor-hearing rats that were fed a control diet exhibited hypoglutamine mia and a 2.3-fold increase in the activity of system n. Glutamine die tary supplementation produced blood glutamine levels that were similar in both tumor-bearing and nontumor-hearing rats, apparently abrogatin g the increase in system n activity that was observed in tumor-bearing rats that were not fed supplemental glutamine, Tumor-bearing animals receiving supplemental glutamine had a decreased number of system n ca rriers (V-max) in the hepatic plasma membrane compared to that of tumo r-bearing animals receiving a control diet; this apparently abrogated the glutamine efflux rate. Glutamine feeding did not alter system n ac tivity in nontumor-bearing controls. CONCLUSIONS: In the tumor-bearing animal model, system n is modulated by the circulating glutamine conc entration. This is the first study that demonstrates the ability of sp ecialized nutrition to ''downregulat'' transport activity in vivo.