Regulation of nitrobenzylthioninosine-sensitive adenosine uptake by cultured kidney cells

Sayós, Joan; Blanco, José Luis Santiago; Ciruela, Franciso; Canela, Enric I.; Mallol, Josefa; Lluı́s, Carme

doi:10.1152/ajprenal.1994.267.5.f758

Cited by 6 publications

(3 citation statements)

References 30 publications

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“…These data suggest that intestinal CNT1 may be regulated by substrate availability [141]. Studies in pig kidney LLC-PK1 cells showed that treatment with chlorophenyl adenosine 3',5'-cyclic monophosphate reduced es activity and NBMPR binding sites in the cells, and the reduction may involve phosphorylation of the transporter molecule or of a protein that interacts with it [143]. Studies in pig kidney LLC-PK1 cells showed that treatment with chlorophenyl adenosine 3',5'-cyclic monophosphate reduced es activity and NBMPR binding sites in the cells, and the reduction may involve phosphorylation of the transporter molecule or of a protein that interacts with it [143].…”

Section: Other Cell Typesmentioning

confidence: 88%

(Section A: Molecular, Structural, and Cellular Biology of Drug Transporters) Mammalian Nucleoside Transporters

Kong

Engel

Wang

2004

CDM

218

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Nucleoside transporters mediate cellular uptake of physiologic nucleosides for nucleic acid synthesis in the salvage pathways in many cell types. These transporters also play an important role in in vivo disposition and intracellular targeting of many nucleoside analogs used in anticancer and antiviral drug therapy. In mammalian cells, there are two major nucleoside transporter gene families: the equilibrative nucleoside transporters (ENTs) and the concentrative nucleoside transporters (CNTs). The ENTs are facilitated carrier proteins and the CNTs are Na(+)-dependent secondary active transporters. Recent molecular cloning of a number of ENT and CNT transporters has greatly advanced our understanding of the molecular and cellular mechanisms by which nucleosides and nucleoside analogs are transported across biological membranes. In this manuscript, we review the structure, function, tissue distribution, and cellular localization of various cloned mammalian nucleoside transporters. Information on transporter interaction with various nucleoside drugs and analogs is presented. Current knowledge on the regulation of nucleoside transporters in various cell types and tissues is reviewed. The therapeutic significance of nucleoside transporters is discussed along with emerging data from recent clinical studies.

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Section: Other Cell Typesmentioning

confidence: 88%

(Section A: Molecular, Structural, and Cellular Biology of Drug Transporters) Mammalian Nucleoside Transporters

Kong

Engel

Wang

2004

CDM

218

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“…Other signal molecules, such as cytokines and pancreatic hormones, modulate nucleoside transport by activating protein kinases. Activation of protein kinase C affects nucleoside transport in chromaffin cells [85] and neuroblastoma cells [86], while protein kinase A inhibits the equilibrative uptake of adenosine in cultured kidney cells [87] and neuroblastoma cells [86]. In human B lymphocytes, tumor necrosis factor‐α activates concentrative transport and decreases equilibrative transport of uridine by activating protein kinase C [88].…”

Section: Pentose Phosphates As a Carbon And An Energy Sourcementioning

confidence: 99%

Pentose phosphates in nucleoside interconversion and catabolism

et al. 2006

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Pentose phosphates are heterocyclic, five-membered, oxygen-containing phosphorylated ring structures, with ribose-5-phosphate (Rib-5-P) and 2-deoxyribose-5-phosphate (deoxyRib-5-P) being basal structures of ribonucleotides and deoxyribonucleotides, respectively, and 5-phosphoribosyl-1-pyrophosphate (PRPP) the common precursor of both de novo and 'salvage' synthesis of nucleotides. Two main pathways are involved in pentose phosphate biosynthesis (Fig. 1). In the oxidative branch of the pentose phosphate pathway, Rib-5-P is generated from glucose-6-phosphate. In the phosphorylase-mediated pathway, deoxyribose-1- Ribose phosphates are either synthesized through the oxidative branch of the pentose phosphate pathway, or are supplied by nucleoside phosphorylases. The two main pentose phosphates, ribose-5-phosphate and ribose-1-phosphate, are readily interconverted by the action of phosphopentomutase. Ribose-5-phosphate is the direct precursor of 5-phosphoribosyl-1-pyrophosphate, for both de novo and 'salvage' synthesis of nucleotides. Phosphorolysis of deoxyribonucleosides is the main source of deoxyribose phosphates, which are interconvertible, through the action of phosphopentomutase.The pentose moiety of all nucleosides can serve as a carbon and energy source. During the past decade, extensive advances have been made in elucidating the pathways by which the pentose phosphates, arising from nucleoside phosphorolysis, are either recycled, without opening of their furanosidic ring, or catabolized as a carbon and energy source. We review herein the experimental knowledge on the molecular mechanisms by which (a) ribose-1-phosphate, produced by purine nucleoside phosphorylase acting catabolically, is either anabolized for pyrimidine salvage and 5-fluorouracil activation, with uridine phosphorylase acting anabolically, or recycled for nucleoside and base interconversion; (b) the nucleosides can be regarded, both in bacteria and in eukaryotic cells, as carriers of sugars, that are made available though the action of nucleoside phosphorylases. In bacteria, catabolism of nucleosides, when suitable carbon and energy sources are not available, is accomplished by a battery of nucleoside transporters and of inducible catabolic enzymes for purine and pyrimidine nucleosides and for pentose phosphates. In eukaryotic cells, the modulation of pentose phosphate production by nucleoside catabolism seems to be affected by developmental and physiological factors on enzyme levels.Abbreviations

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“…However, in some non-neural es-systems and Na + -dependent processes the regulation by phosphorylation/dephosphorylation seems to present some variability [Lee, 1994;Sayós et al, 1994;Coe et al, 1996;Soler et al, 1998]. Furthermore, the non-neural es-transporter of microvascular endothelial cells from the adrenal medulla was not regulated to any extent by protein kinases A and C [Sen et al, 1996], indicating that not all the es-sytems are susceptible to regulation by the same kind of mechanisms.…”

Section: Regulatory Studies Of Nucleoside Transporters: Allosteric Momentioning

confidence: 99%

Nucleoside transporter and nucleotide vesicular transporter: Two examples of mnemonic regulation

Sen

Delicado

Gualix

2001

Drug Development Research

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According to their relevant roles in the regulation and availability of extracellular levels of purinergic signals, the nucleoside transporter and the nucleotide vesicular transporter are subject to acute regulation. The plasma membrane nucleoside transporter has been shown to exhibit several regulatory mechanisms, such as regulation by long-term signals, phosphorylation/dephosphorylation processes, and allosteric modulation. The present work reviews studies concerning allosteric modulation of nucleoside and nucleotide vesicular transporters, as the first reported examples of mnemonic behavior in transporter proteins, presenting kinetic and allosteric cooperativity. This fact implies that the protein can exhibit different conformations, each one with specific kinetic parameters. Transport substrates are able to induce slow conformational changes between the different forms of the transporter. This kinetic mechanism can provide several physiological advantages, since it allows strict control of transport capacity by changes in substrate concentrations. This allosteric modulation has been confirmed in several experimental models, the nucleoside transporter in chromaffin and endothelial cells from adrenal medulla and the nucleotide vesicular transporter in the chromaffin cell granules and rat brain synaptic vesicles. Taking into account these considerations, the mnemonic regulation described here could be a widespread mechanism among transporter proteins. Drug Dev. Res. 52:11-21, 2001.

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Regulation of nitrobenzylthioninosine-sensitive adenosine uptake by cultured kidney cells

Cited by 6 publications

References 30 publications

(Section A: Molecular, Structural, and Cellular Biology of Drug Transporters) Mammalian Nucleoside Transporters

(Section A: Molecular, Structural, and Cellular Biology of Drug Transporters) Mammalian Nucleoside Transporters

Pentose phosphates in nucleoside interconversion and catabolism

Nucleoside transporter and nucleotide vesicular transporter: Two examples of mnemonic regulation

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