Valdés R, Ortega M A, Casado F J, Felipe A, Gil A, Sánchez-Pozo A, Pastor-Anglada M
Departament de Bioquímica i Biologia Molecular, University of Barcelona, Barcelona, Spain.
Gastroenterology. 2000 Dec;119(6):1623-30. doi: 10.1053/gast.2000.20183.
BACKGROUND & AIMS: 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.
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.
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.
Substrate availability modulates nucleoside transporter expression (CNT1) in rat jejunum in vivo.
浓缩核苷转运体CNT1（嘧啶偏好型）和CNT2（嘌呤偏好型）可能参与抗病毒和化学疗法中核苷类药物的摄取。已研究了核苷载体异构体表达是否受营养可利用性调节的可能性。
通过蛋白质印迹分析确定CNT1和CNT2的组织分布。然后研究48小时饥饿对CNT表达的影响。在喂食和饥饿大鼠的空肠刷状缘质膜囊泡中测量核苷转运体表达和摄取活性。随后在第二种营养缺乏模型中确定核苷转运体的表达：喂食含或不含核苷酸的纯化饮食10天的大鼠。
CNT1和CNT2核苷转运体在比信使RNA分布分析预期更广泛的多种组织中表达。CNT1在小肠中对营养可利用性敏感，因此，来自禁食48小时大鼠的空肠刷状缘膜囊泡显示CNT1表达增加，且钠依赖性胸苷和吉西他滨摄取增强。缺乏核苷酸的半纯化饮食喂养可模拟这种效应。
底物可利用性在体内调节大鼠空肠中的核苷转运体表达（CNT1）。
