Intestinal extraction of circulating
glutamine across the basolateral membrane is diminished in the
tumor-bearing rat (TBR). This study was designed to investigate the effects of progressive malignant growth on brush border
glutamine transport in order to gain further insight into the adaptive/regulatory changes in intestinal
glutamine metabolism that occur in the
tumor-bearing rat. Fischer 344 rats (225 +/- 5 g) were implanted with
fibrosarcoma cells and were studied at various time points after implantation when the
tumors comprised 7%, 20%, and 29% of total
body weight. Control and
tumor-bearing rats were pair-fed throughout the study. Jejunal brush border membrane vesicles (BBMVs) were prepared by
magnesium aggregation/differential centrifugation and transport of radioactively labeled
L-glutamine,
L-leucine,
L-alanine, and
D-glucose by BBMVs was measured using a Millipore filtration technique. BBMVs were enriched 15-fold in
alkaline phosphatase, indicating brush border vesicle purity. Uptake of all substrates occurred into an osmotically active space, exhibited overshoots, and had similar 1-hr equilibrium values. The rate of
glutamine uptake by BBMVs from all
tumor-bearing rats was significantly greater than controls, regardless of
tumor size. The increase in transport activity was not due to a change in carrier affinity but rather to an increase in maximal transport velocity. In rats with small
tumors (7% of
body weight), the Vmax was 431 +/- 40 pmole/mg
protein/10 sec compared to 259 +/- 30 in control animals (P less than 0.01). In marked contrast, the mean transport of
alanine was diminished in BBMVs from TBR (31 +/- 3 pmole/mg
protein/10 sec in TBR vs 23 +/- 2 in controls, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)