Tissue Distribution of Concentrative and Equilibrative Nucleoside Transporters in Male and Female Rats and Mice

Abstract

ABSTRACT:Concentrative nucleoside transporters (Cnts) and equilibrative nucleoside transporters (Ents) have essential physiological functions and are important in disposition of anticancer and antiviral nucleoside analogs. Information on tissue distribution of Cnts and Ents in rodents is sparse. Thus, the present study aimed to determine the distribution of Cnt1-3 and Ent1-3 transcripts in 19 tissues of Sprague-Dawley rats and C57BL/6 mice of both genders. These six transcripts were quantified using the branched DNA signal amplification assay. Cnt1 transcripts were highest in small intestine, followed by kidney and testes, with similar expression in both species. Cnt2 mRNA was expressed highest in the small intestine of both rats and mice, intermediate in liver of rats but not in mice, and lower in thymus and spleen of both species. Cnt3 mRNA has marked species differences, with the highest expression in lung of rats but uterus of mice. Ent1 mRNA was most highly expressed in testes and lung of both species. Ent1 mRNA was highly expressed in liver and pituitary of mice, but not in rats. Ent2 mRNA was highly expressed in testes and brain of both species. Ent3 mRNA was highest in kidney, followed by testes, in both species. Significant gender differences were observed in kidney (mouse) and heart (rat). These studies demonstrate that in general, tissue distribution of Cnt and Ent is similar in rats and mice. However, a few important species and gender differences do exist, which could be responsible for related differences in efficacy and toxicity of substrates for these transporters.

Antibody-mediated enzyme replacement therapy targeting both lysosomal and cytoplasmic glycogen in Pompe disease

“…Little 150 kDa FabGAA was detected in liver where the protein existed predominately as the 76 kDa lysosomal form (Fig. 3f), which is consistent with low expression of ENT2 and high expression of M6PR in this tissue [20,30]. At 9 h, the amount of fulllength FabGAA was significantly reduced while the 76 kDa form remained unchanged in heart and skeletal muscles (Fig.…”

“…In addition, a recent study demonstrated that ERT with 3E10Fv-MTM1 fusion protein improved muscle function and pathology in mice with X-linked myotubular myopathy [17]. 3E10 penetrates cells via equilibrative nucleoside transporter 2 (ENT2) [18] that is expressed at high levels in human and rodent skeletal muscles and heart [19,20], making it an ideal vehicle for cytoplasmic delivery of therapeutic GAA in muscle tissues of Pompe disease. A 3E10-GAA fusion should enable ENT2-mediated uptake to clear extra-lysosomal glycogen in muscle fibers while retaining the ability to degrade lysosomal glycogen via M6PR-mediated uptake.…”

Transport Mechanisms of Nucleosides and Nucleoside Analogues ReverseTranscriptase Inhibitors in the Brain

“…Overall, this study concluded that activation of JNK-cJun pathway negatively regulates mENT1 (Leisewitz et al, 2011). Current knowledge suggest that ENT3 is present in most tissues, including brain (Lu et al, 2004). It was found to co-localize with lysosomal markers and showed broad selectivity and low affinity towards the naturally occurring nucleosides and was unaffected by micromolar NBMPR, dipyridamole or dilazep .…”

“…Amount of CNT1 mRNA in the brain was less abundant than in epithelia (Lu et al, 2004). In the brain, CNT1 mRNA was detected by in cerebral cortex, hypothalamus, hippocampus, cerebellum and choroid plexus (Lu et al, 2004).…”

“…In the brain, CNT1 mRNA was detected by in cerebral cortex, hypothalamus, hippocampus, cerebellum and choroid plexus (Lu et al, 2004). Rat astrocytes in primary culture express rCNT1 transcript, as revealed by RT-PCR, but the abundance was very low; however, rCNT1 protein was detected in these cells by immunoblotting (Redzic et al 2010b).…”