Nucleoside transporters: from scavengers to novel therapeutic targets

King, Anne E.; Ackley, Michael A.; Cass, Carol E.; Young, James D.; Baldwin, Stephen A.

doi:10.1016/j.tips.2006.06.004

Cited by 260 publications

(249 citation statements)

References 67 publications

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“…Both ENTs and CNTs are expressed in highly metabolically active tissues, including the brain. However, they differ in selectivity, kinetics, regulation and subcellular distribution (King et al, 2006).…”

Section: Adenosine Transportmentioning

confidence: 99%

“…The CNT family demonstrates a more distinct selectivity in nucleoside transporting than the ENT family. Most CNTs show a pyrimidine preference with similar affinity to adenosine molecules, yet the rate of adenosine transport by CNT1 is much lower than the rate of pyrimidine transport and CNT1 displays a much lower turnover number of molecules per second than ENT1 (King et al, 2006). Interestingly, acute ethanol treatment in neuronal cells is known to increase extracellular adenosine, whereas chronic exposure no longer increases adenosine.…”

Section: Adenosine Transportmentioning

confidence: 99%

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Adenosine Signaling in Striatal Circuits and Alcohol Use Disorders

Nam

Bruner

Choi

2013

Molecules and Cells

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Adenosine signaling has been implicated in the pathophysiology of alcohol use disorders and other psychiatric disorders such as anxiety and depression. Numerous studies have indicated a role for A1 receptors (A1R) in acute ethanol-induced motor incoordination, while A2A receptors (A2AR) mainly regulate the rewarding effect of ethanol in mice. Recent findings have demonstrated that dampened A2AR-mediated signaling in the dorsomedial striatum (DMS) promotes ethanol-seeking behaviors. Moreover, decreased A2AR function is associated with decreased CREB activity in the DMS, which enhances goal-oriented behaviors and contributes to excessive ethanol drinking in mice. Interestingly, caffeine, the most commonly used psychoactive substance, is known to inhibit both the A1R and A2AR. This dampened adenosine receptor function may mask some of the acute intoxicating effects of ethanol. Furthermore, based on the fact that A2AR activity plays a role in goal-directed behavior, caffeine may also promote ethanol-seeking behavior. The A2AR is enriched in the striatum and exclusively expressed in striatopallidal neurons, which may be responsible for the regulation of inhibitory behavioral control over drug rewarding processes through the indirect pathway of the basal ganglia circuit. Furthermore, the antagonistic interactions between adenosine and dopamine receptors in the striatum also play an integral role in alcoholism and addiction-related disorders. This review focuses on regulation of adenosine signaling in striatal circuits and the possible implication of caffeine in goal-directed behaviors and addiction.

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Section: Adenosine Transportmentioning

confidence: 99%

Section: Adenosine Transportmentioning

confidence: 99%

Adenosine Signaling in Striatal Circuits and Alcohol Use Disorders

Nam

Bruner

Choi

2013

Molecules and Cells

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“…The very short half-life of adenosine in blood and other fluids, typically measured in seconds, limits the activity of adenosine as an extracellular signal and maintenance of adenosine levels in extracellular fluids is the result of an equilibrium between production and consumption [23]. A basal level of extracellular adenosine is maintained between 30 and 200 nM [24,25]. Extracellular adenosine is cytoprotective, increases oxygen supply, angiogenesis, and protects against ischemic damage [26].…”

Section: Adenosine Signalingmentioning

confidence: 99%

Regulation of bone and cartilage by adenosine signaling

Strazzulla

Cronstein

2016

Purinergic Signalling

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There is growing recognition that bone serves important endocrine and immunologic functions that are compromised in several disease states. While many factors are known to affect bone metabolism, recent attention has focused on investigating the role of purinergic signaling in bone formation and regulation. Adenosine is a purine nucleoside produced intracellularly and extracellularly in response to stimuli such as hypoxia and inflammation, which then interacts with P1 receptors. Numerous studies have suggested that these receptors play a pivotal role in osteoblast, osteoclast, and chondrocyte differentiation and function. This review discusses the various ways by which adenosine signaling contributes to bone and cartilage homeostasis, while incorporating potential therapeutic applications of these signaling pathways.

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“…Consequently, the energy status of hypoxic cells is precarious and leads to high intracellular levels of adenosine as ATP is broken down by the sequential actions of adenosine kinase and cytosolic 5 0 -nucleotidase (Sala-Newby et al, 1999). Adenosine can enter the tumor microenvironment through equilibrative nucleoside transporters (King et al, 2006) or be formed by extracellular ecto-phosphopyrases (such as CD39) and ecto-5 0 -nucleotidases (such as CD73) when necrotic cells spill their intracellular contents (Lasley et al, 1999). High levels of adenosine in the tumor microenvironment (Blay et al, 1997) may be a major obstacle to the development of TLR tolerization in cancer cells as adenosine is an especially strong negative regulator of TLR signaling, prevents TNF-a synthesis after initial TLR stimulation and accounts for poor responses of neonates to endotoxin in vivo (Levy et al, 2006).…”

Section: Adenosinementioning

confidence: 99%

“…Adenosine can be taken up through concentrative, as well as equilibrative, transporters (King et al, 2006) and enter the cytoplasm where it has a number of possible fates that may profoundly affect subsequent responses to TLR agonists. It can be degraded to inosine via adenosine deaminase, and subsequently to uric acid, without much impact on TLR signaling.…”

Section: Adenosinementioning

confidence: 99%