Nucleoside Transporters of Mammalian Cells

Cass, Carol E.; Young, James D.; Baldwin, Stephen A.; Cabrita, Miguel A.; Graham, Kathryn; Griffiths, Mark; Jennings, Lori L.; Mackey, John R.; Ng, Amy M. L.; Ritzel, Mabel W.L.; Vickers, Mark F.; Yao, Sylvia Y. M.

doi:10.1007/0-306-46812-3_12

Cited by 121 publications

(76 citation statements)

References 105 publications

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“…Since most nucleosides and their analogues are relatively hydrophilic and thus cannot readily pass the plasma membrane, nucleoside transporters are essential in adjusting extra-and intracellular adenosine levels (Cass et al, 1999). In addition, nucleoside transporters play an important role in the transport of antiviral nucleoside derivatives (Yamamoto et al, 2007).…”

Section: Nucleoside Transportersmentioning

confidence: 99%

The adenosine kinase hypothesis of epileptogenesis

Boison

2008

Progress in Neurobiology

200

209

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Current therapies for epilepsy are largely symptomatic and do not affect the underlying mechanisms of disease progression, i.e. epileptogenesis. Given the large percentage of pharmacoresistant chronic epilepsies, novel approaches are needed to understand and modify the underlying pathogenetic mechanisms. Although different types of brain injury (e.g. status epilepticus, traumatic brain injury, stroke) can trigger epileptogenesis, astrogliosis appears to be a homotypic response and hallmark of epilepsy. Indeed, recent findings indicate that epilepsy might be a disease of astrocyte dysfunction. This review focuses on the inhibitory neuromodulator and endogenous anticonvulsant adenosine, which is largely regulated by astrocytes and its key metabolic enzyme adenosine kinase (ADK). Recent findings support the "ADK hypothesis of epileptogenesis": (i) Mouse models of epileptogenesis suggest a sequence of events leading from initial downregulation of ADK and elevation of ambient adenosine as an acute protective response, to changes in astrocytic adenosine receptor expression, to astrocyte proliferation and hypertrophy (i.e. astrogliosis), to consequential overexpression of ADK, reduced adenosine and -finally -to spontaneous focal seizure activity restricted to regions of astrogliotic overexpression of ADK. (ii) Transgenic mice overexpressing ADK display increased sensitivity to brain injury and seizures. (iii) Inhibition of ADK prevents seizures in a mouse model of pharmacoresistant epilepsy. (iv) Intrahippocampal implants of stem cells engineered to lack ADK prevent epileptogenesis. Thus, ADK emerges both as a diagnostic marker to predict, as well as a prime therapeutic target to prevent, epileptogenesis.

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Section: Nucleoside Transportersmentioning

confidence: 99%

The adenosine kinase hypothesis of epileptogenesis

Boison

2008

Progress in Neurobiology

200

209

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“…Six functional subtypes of CNT processes (Gutierrez et al, 1992;Belt et al, 1993;Giacomini, 1993, 1994;Paterson et al, 1993;Cass, 1995;Griffith and Jarvis, 1996;Flanagan and Meckling-Gill, 1997;Ritzel et al, 1997Ritzel et al, , 1998Ritzel et al, , 2001aCass et al, 1999) have been described in human cells or tissues. The three best characterized CNTs are Na þ -nucleoside cotransporters and are termed cit, cif and cib to indicate that they are concentrative, insensitive to NBMPR and accept as permeants, respectively, pyrimidine nucleosides, purine nucleosides or both pyrimidine and purine nucleosides.…”

Section: Functional Characterizationmentioning

confidence: 99%

Nucleoside anticancer drugs: the role of nucleoside transporters in resistance to cancer chemotherapy

et al. 2003

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The clinical efficacy of anticancer nucleoside drugs depends on a complex interplay of transporters mediating entry of nucleoside drugs into cells, efflux mechanisms that remove drugs from intracellular compartments and cellular metabolism to active metabolites. Nucleoside transporters (NTs) are important determinants for salvage of preformed nucleosides and mediated uptake of antimetabolite nucleoside drugs into target cells. The focus of this review is the two families of human nucleoside transporters (hENTs, hCNTs) and their role in transport of cytotoxic chemotherapeutic nucleoside drugs. Resistance to anticancer nucleoside drugs is a major clinical problem in which NTs have been implicated. Single nucleotide polymorphisms (SNPs) in drug transporters may contribute to interindividual variation in response to nucleoside drugs. In this review, we give an overview of the functional and molecular characteristics of human NTs and their potential role in resistance to nucleoside drugs and discuss the potential use of genetic polymorphism analyses for NTs to address drug resistance.

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“…Furthermore, [ -free conditions and TTX; therefore, carrier-mediated release was taken into account as a possible mechanism. Among various membrane transporters, those that are able to transport nucleotides and nucleosides, ABC transporters (Schwiebert, 1999) and nucleoside transporters (Thorn & Jarvis, 1996;Cass et al, 1999), seemed to be potential candidates for the underlying carrier. Nucleoside transporters form two different families: the CNT transporters which function in a concentrative way, and utilize an Na + as a cotransport (Ritzel et al, 2001), and ENT transporters, which function in an equilibrative way and independent of Na + .…”

Section: B Sperlágh Et Almentioning

confidence: 99%

Homo‐ and heteroexchange of adenine nucleotides and nucleosides in rat hippocampal slices by the nucleoside transport system

Sperlágh

Szabó

Erdélyi

et al. 2003

British J Pharmacology

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1 Here, we investigated how nucleotides and nucleosides affect the release of tritiated purines and endogenous adenosine 5 0 -triphosphate (ATP) from superfused rat hippocampal slices.2 ATP elicited concentration-dependent [ 4 Reverse transcription-coupled-polymerase chain reaction analysis revealed that mRNAs encoding a variety of P2X and P2Y receptor proteins are expressed in the rat hippocampus. Nevertheless, neither P2 receptor (i.e. pyridoxal-5-phosphate-6-azophenyl-2 0 ,4 0 -disulphonic acid, 30 mM, suramin, 300 mM and reactive blue 2, 10 mM), nor adenosine receptor (8-cyclopentyl-1,3-dipropylxanthine, 250 nM and dimethyl-1-propargylxanthine, 250 nM) antagonists modified the effect of ATP (300 mM) to evoke [ 3 H]purine release. 5 The nucleoside transport inhibitors, dipyridamole (10 mM), nitrobenzylthioinosine (10 mM) and adenosine deaminase (2 -10 U ml 6 In summary, we found that ATP and other nucleotides and nucleosides promote the release of one another and themselves by the nucleoside transport system. This action could have relevance during physiological and pathological elevation of extracellular purine levels high enough to reverse the nucleoside transporter.

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Nucleoside Transporters of Mammalian Cells

Cited by 121 publications

References 105 publications

The adenosine kinase hypothesis of epileptogenesis

The adenosine kinase hypothesis of epileptogenesis

Nucleoside anticancer drugs: the role of nucleoside transporters in resistance to cancer chemotherapy

Homo‐ and heteroexchange of adenine nucleotides and nucleosides in rat hippocampal slices by the nucleoside transport system

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