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Molecular cloning and functional characterization of inhibitor-sensitive (mENT1) and inhibitor-resistant (mENT2) equilibrative nucleoside transporters from mouse brain.
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Mammalian cells express at least two subtypes of equilibrative nucleoside transporters, i.e. ENT1 and ENT2, which can be distinguished functionally by their sensitivity and resistance respectively to inhibition by nitrobenzylthioinosine. The ENT1 transporters exhibit distinctive species differences in their sensitivities to inhibition by dipyridamole, dilazep and draflazine (human>mouse>rat). A comparison of the ENT1 structures in the three species would facilitate the identification of the regions involved in the actions of these cardioprotective agents. We now report the molecular cloning and functional expression of the murine (m)ENT1 and mENT2 transporters. mENT1 and mENT2 encode proteins containing 458 and 456 residues respectively, with a predicted 11-transmembrane-domain topology. mENT1 has 88% and 78% amino acid identity with rat ENT1 and human ENT1 respectively; mENT2 is more highly conserved, with 94% and 88% identity with rat ENT2 and human ENT2 respectively. We have also isolated two additional distinct cDNAs that encode proteins similar to mENT1; these probably represent distinct mENT1 isoforms or alternative splicing products. One cDNA encodes a protein with two additional amino acids (designated mENT1b) that adds a potential protein kinase CK2 phosphorylation site in the central intracellular loop of the transporter, and is similar, in this regard, to the human and rat ENT1 orthologues. The other cDNA has a 5'-untranslated region sequence that is distinct from that of full-length mENT1. Microinjection of mENT1, mENT1b or mENT2 cRNA into Xenopus oocytes resulted in enhanced uptake of [(3)H]uridine by the oocytes relative to that seen in water-injected controls. mENT1-mediated, but not mENT2-mediated, [(3)H]uridine uptake was inhibited by nitrobenzylthioinosine and dilazep. Dipyridamole inhibited both mENT1 and mENT2, but was significantly more effective against mENT1. Adenosine inhibited both systems with a similar potency, as did a range of other purine and pyrimidine nucleosides. These results are compatible with the known characteristics of the native mENT1 and mENT2 transporters.
Abd-Elfattah,
Differential cardioprotection with selective inhibitors of adenosine metabolism and transport: role of purine release in ischemic and reperfusion injury.
1998, Pubmed
Abd-Elfattah,
Differential cardioprotection with selective inhibitors of adenosine metabolism and transport: role of purine release in ischemic and reperfusion injury.
1998,
Pubmed Arch,
The control of the metabolism and the hormonal role of adenosine.
1978,
Pubmed Baer,
Potencies of mioflazine and its derivatives as inhibitors of adenosine transport in isolated erythrocytes from different species.
1990,
Pubmed Baldwin,
Nucleoside transporters: molecular biology and implications for therapeutic development.
1999,
Pubmed Belt,
Nucleoside transport in normal and neoplastic cells.
1993,
Pubmed Böhm,
Studies of the nucleoside transporter inhibitor, draflazine, in the human myocardium.
1994,
Pubmed Burke,
Interaction of 2',2'-difluorodeoxycytidine (gemcitabine) and formycin B with the Na+-dependent and -independent nucleoside transporters of Ehrlich ascites tumor cells.
1998,
Pubmed Cass,
Recent advances in the molecular biology of nucleoside transporters of mammalian cells.
1998,
Pubmed
,
Xenbase Crawford,
Cloning of the human equilibrative, nitrobenzylmercaptopurine riboside (NBMPR)-insensitive nucleoside transporter ei by functional expression in a transport-deficient cell line.
1998,
Pubmed Deckert,
Adenosine uptake site heterogeneity in the mammalian CNS? Uptake inhibitors as probes and potential neuropharmaceuticals.
1988,
Pubmed Delicado,
Effects of phorbol esters and secretagogues on nitrobenzylthioinosine binding to nucleoside transporters and nucleoside uptake in cultured chromaffin cells.
1991,
Pubmed Ely,
Protective effects of adenosine in myocardial ischemia.
1992,
Pubmed Farinelli,
Neuroprotective actions of dipyridamole on cultured CNS neurons.
1998,
Pubmed Flameng,
A new concept of long-term donor heart preservation: nucleoside transport inhibition.
1991,
Pubmed Griffith,
Differential inhibition of nucleoside transport systems in mammalian cells by a new series of compounds related to lidoflazine and mioflazine.
1990,
Pubmed Griffith,
Nucleoside and nucleobase transport systems of mammalian cells.
1996,
Pubmed Griffiths,
Molecular cloning and characterization of a nitrobenzylthioinosine-insensitive (ei) equilibrative nucleoside transporter from human placenta.
1997,
Pubmed
,
Xenbase Griffiths,
Cloning of a human nucleoside transporter implicated in the cellular uptake of adenosine and chemotherapeutic drugs.
1997,
Pubmed
,
Xenbase Hammond,
Species differences in the binding of [3H]nitrobenzylthioinosine to the nucleoside transport system in mammalian central nervous system membranes: evidence for interconvertible conformations of the binding site/transporter complex.
1985,
Pubmed Hammond,
Solubilization and reconstitution of a nucleoside-transport system from Ehrlich ascites-tumour cells.
1989,
Pubmed Hammond,
Differential uptake of [3H]guanosine by nucleoside transporter subtypes in Ehrlich ascites tumour cells.
1992,
Pubmed Hammond,
Interaction of a series of draflazine analogues with equilibrative nucleoside transporters: species differences and transporter subtype selectivity.
2000,
Pubmed Hammond,
Comparative pharmacology of the nitrobenzylthioguanosine-sensitive and -resistant nucleoside transport mechanisms of Ehrlich ascites tumor cells.
1991,
Pubmed Huang,
Functional expression of Na(+)-dependent nucleoside transport systems of rat intestine in isolated oocytes of Xenopus laevis. Demonstration that rat jejunum expresses the purine-selective system N1 (cif) and a second, novel system N3 having broad specificity for purine and pyrimidine nucleosides.
1993,
Pubmed
,
Xenbase Kwong,
Enzymic cleavage as a probe of the molecular structures of mammalian equilibrative nucleoside transporters.
1993,
Pubmed Lee,
Induction of the differentiation of HL-60 cells by phorbol 12-myristate 13-acetate activates a Na(+)-dependent uridine-transport system. Involvement of protein kinase C.
1991,
Pubmed Lee,
Decrease in equilibrative uridine transport during monocytic differentiation of HL-60 leukaemia: involvement of protein kinase C.
1994,
Pubmed Mackey,
Nucleoside transport and its significance for anticancer drug resistance.
1998,
Pubmed Mani,
Demonstration of equilibrative nucleoside transporters (hENT1 and hENT2) in nuclear envelopes of cultured human choriocarcinoma (BeWo) cells by functional reconstitution in proteoliposomes.
1998,
Pubmed Mayer,
SH3 domains. Minding your p's and q's.
1995,
Pubmed Miras-Portugal,
Control of nucleoside transport in neural cells. Effect of protein kinase C activation.
1991,
Pubmed Mubagwa,
Role of adenosine in the heart and circulation.
1996,
Pubmed Murray,
The biological significance of purine salvage.
1971,
Pubmed Musacchio,
High-resolution crystal structures of tyrosine kinase SH3 domains complexed with proline-rich peptides.
1994,
Pubmed Ogbunude,
Competition of nucleoside transport inhibitors with binding of 6-[(4-nitrobenzyl)-mercapto]purine ribonucleoside to intact erythrocytes and ghost membranes from different species.
1990,
Pubmed Paul,
Inhibitors of nucleoside transport. A structure-activity study using human erythrocytes.
1975,
Pubmed Plagemann,
Species differences in sensitivity of nucleoside transport in erythrocytes and cultured cells to inhibition by nitrobenzylthioinosine, dipyridamole, dilazep and lidoflazine.
1988,
Pubmed Rongen,
Hemodynamic and neurohumoral effects of various grades of selective adenosine transport inhibition in humans. Implications for its future role in cardioprotection.
1995,
Pubmed Shank,
Adenosine transport by rat and guinea pig synaptosomes: basis for differential sensitivity to transport inhibitors.
1990,
Pubmed Soler,
Regulation of nucleoside transport by lipopolysaccharide, phorbol esters, and tumor necrosis factor-alpha in human B-lymphocytes.
1998,
Pubmed Staub,
Nucleoside transport and metabolism in lymphocytes, polymorphonuclear cells and cerebral synaptosomes.
1994,
Pubmed Sundaram,
Chimeric constructs between human and rat equilibrative nucleoside transporters (hENT1 and rENT1) reveal hENT1 structural domains interacting with coronary vasoactive drugs.
1998,
Pubmed
,
Xenbase Van Belle,
Nucleoside transport inhibition: a therapeutic approach to cardioprotection via adenosine?
1993,
Pubmed Vickers,
Functional production and reconstitution of the human equilibrative nucleoside transporter (hENT1) in Saccharomyces cerevisiae. Interaction of inhibitors of nucleoside transport with recombinant hENT1 and a glycosylation-defective derivative (hENT1/N48Q).
1999,
Pubmed von Lubitz,
Adenosine: a prototherapeutic concept in neurodegeneration.
1995,
Pubmed Williams,
A mammalian delayed-early response gene encodes HNP36, a novel, conserved nucleolar protein.
1995,
Pubmed Williams,
The human HNP36 gene is localized to chromosome 11q13 and produces alternative transcripts that are not mutated in multiple endocrine neoplasia, type 1 (MEN I) syndrome.
1997,
Pubmed Yao,
Molecular cloning and functional characterization of nitrobenzylthioinosine (NBMPR)-sensitive (es) and NBMPR-insensitive (ei) equilibrative nucleoside transporter proteins (rENT1 and rENT2) from rat tissues.
1997,
Pubmed
,
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