Selective stimulation of brush border glutamine transport in the tumor-bearing rat.
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)
Salloum
R M
RM
Department of Surgery, University of Florida College of Medicine, Gainesville 32610.
Copeland
E M
EM
Bland
K I
KI
Souba
W W
WW
D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism*; D066298:In Vitro Techniques; D007408:Intestinal Absorption; D007700:Kinetics; D008871:Microvilli / Q000378:metabolism*; D009374:Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344
D002352:Carrier Proteins; C037853:glutamine transport proteins; D005973:Glutamine