Nutritional regulation of nucleoside transporter expression in rat small intestine.
OBJECTIVE
Concentrative nucleoside transporters CNT1 (pyrimidine preferring) and CNT2 (purine preferring) may be involved in the uptake of nucleoside-derived drugs used in antiviral and chemical therapies. The possibility that nucleoside carrier isoform expression is modulated by nutrient availability has been studied.


METHODS
CNT1 and CNT2 tissue distribution was determined by Western blot analysis. The effect of 48-hour starvation on CNT expression was then studied. Nucleoside transporter expression and uptake activity were measured in jejunal brush border plasma membrane vesicles from fed and starved rats. The expression of nucleoside transporters was later determined in a second model of nutrient deficiency: rats fed a purified diet with or without nucleotides for 10 days.


RESULTS
CNT1 and CNT2 nucleoside transporters were expressed in a wider variety of tissues than expected from messenger RNA distribution analysis. CNT1 was sensitive to nutrient availability in small intestine and, accordingly, jejunal brush border membrane vesicles from 48-hour-fasted rats showed increased expression of CNT1 and enhanced Na(+)-dependent thymidine and gemcitabine uptake. This effect was mimicked by feeding semipurified diets lacking nucleotides.


CONCLUSIONS
Substrate availability modulates nucleoside transporter expression (CNT1) in rat jejunum in vivo.
Valdés
R
R
Departament de Bioquímica i Biologia Molecular, University of Barcelona, Barcelona, Spain.
Ortega
M A
MA
Casado
F J
FJ
Felipe
A
A
Gil
A
A
Sánchez-Pozo
A
A
Pastor-Anglada
M
M
D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D004032:Diet; D007106:Immune Sera / Q000276:immunology; D007421:Intestine, Small / Q000378:metabolism*; D007583:Jejunum / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D008871:Microvilli / Q000378:metabolism; D033703:Nucleoside Transport Proteins; D009711:Nucleotides / Q000008:administration & dosage; D009842:Oligopeptides / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D013217:Starvation / Q000378:metabolism; D013379:Substrate Specificity; D014018:Tissue Distribution
D002352:Carrier Proteins; D007106:Immune Sera; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D033703:Nucleoside Transport Proteins; D009711:Nucleotides; D009842:Oligopeptides; C065171:cif nucleoside transporter