Enzymatic conversion of ATP to adenosine contributes to ATP-induced inhibition of glutamate release in rat medullary dorsal horn neurons

Choi, In–Hwan; Cho, Jin-Hwa; Lee, Maan‐Gee; Jang, Il‐Sung

doi:10.1016/j.neuropharm.2015.01.020

Cited by 15 publications

(14 citation statements)

References 48 publications

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“…Additionally, previous studies have reported that extracellular ATP regulates cell function by activating ionotropic P2X and metabotropic P2Y receptors. 39 – 41 Thus, we blocked these receptors with pyridoxal phosphate-6-azo (PPADS) and suramin, which are nonselective P2X and P2Y receptor antagonists, respectively. Similar to the EIPA experiment, the ATP levels were decreased by no >20% in both the WT and Alpl +/- MSCs treated with PPADs and suramin (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Previous studies have reported that extracellular ATP regulates cell function by activating ionotropic P2X and metabotropic P2Y receptors. 39 – 41 Additionally, a recent study showed that extracellular ATP in the form of nonhydrolyzable fluorescent NHF-ATP is internalized by macropinocytosis. 26 However, in this study, we observed that neither macropinocytosis nor purinergic receptor signaling could account for the intracellular ATP elevation.…”

Section: Discussionmentioning

confidence: 99%

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Alpl prevents bone ageing sensitivity by specifically regulating senescence and differentiation in mesenchymal stem cells

et al. 2018

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Mutations in the liver/bone/kidney alkaline phosphatase (Alpl) gene cause hypophosphatasia (HPP) and early-onset bone dysplasia, suggesting that this gene is a key factor in human bone development. However, how and where Alpl acts in bone ageing is largely unknown. Here, we determined that ablation of Alpl induces prototypical premature bone ageing characteristics, including bone mass loss and marrow fat gain coupled with elevated expression of p16INK4A (p16) and p53 due to senescence and impaired differentiation in mesenchymal stem cells (MSCs). Mechanistically, Alpl deficiency in MSCs enhances ATP release and reduces ATP hydrolysis. Then, the excessive extracellular ATP is, in turn, internalized by MSCs and causes an elevation in the intracellular ATP level, which consequently inactivates the AMPKα pathway and contributes to the cell fate switch of MSCs. Reactivating AMPKα by metformin treatment successfully prevents premature bone ageing in Alpl+/- mice by improving the function of endogenous MSCs. These results identify a previously unknown role of Alpl in the regulation of ATP-mediated AMPKα alterations that maintain MSC stemness and prevent bone ageing and show that metformin offers a potential therapeutic option.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Alpl prevents bone ageing sensitivity by specifically regulating senescence and differentiation in mesenchymal stem cells

et al. 2018

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“…It has been concluded, based on the use of selective antagonists and A1 receptor-deficient mice, that this inhibitory effect requires localized extracellular catabolism by ectonucleotidases and 'channelling' of the generated adenosine to A1 receptors [231,232]. Similar data were reported also for the rat striatum [233] and medullary dorsal horn neurons [234].…”

Section: Purinergic Modulation Of Glutamatergic Neurotransmissionsupporting

confidence: 53%

Modulation of excitatory neurotransmission by neuronal/glial signalling molecules: interplay between purinergic and glutamatergic systems

Köles

Kató

Hanuska

et al. 2015

Purinergic Signalling

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Glutamate is the main excitatory neurotransmitter of the central nervous system (CNS), released both from neurons and glial cells. Acting via ionotropic (NMDA, AMPA, kainate) and metabotropic glutamate receptors, it is critically involved in essential regulatory functions. Disturbances of glutamatergic neurotransmission can be detected in cognitive and neurodegenerative disorders. This paper summarizes the present knowledge on the modulation of glutamate-mediated responses in the CNS. Emphasis will be put on NMDA receptor channels, which are essential executive and integrative elements of the glutamatergic system. This receptor is crucial for proper functioning of neuronal circuits; its hypofunction or overactivation can result in neuronal disturbances and neurotoxicity. Somewhat surprisingly, NMDA receptors are not widely targeted by pharmacotherapy in clinics; their robust activation or inhibition seems to be desirable only in exceptional cases. However, their fine-tuning might provide a promising manipulation to optimize the activity of the glutamatergic system and to restore proper CNS function. This orchestration utilizes several neuromodulators. Besides the classical ones such as dopamine, novel candidates emerged in the last two decades. The purinergic system is a promising possibility to optimize the activity of the glutamatergic system. It exerts not only direct and indirect influences on NMDA receptors but, by modulating glutamatergic transmission, also plays an important role in glia-neuron communication. These purinergic functions will be illustrated mostly by depicting the modulatory role of the purinergic system on glutamatergic transmission in the prefrontal cortex, a CNS area important for attention, memory and learning.

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“…Postsynaptic A 1 R activation inhibits the activation of glutamatergic N -methyl- d -aspartate receptors (NMDARs) and adenosine binding to A 1 Rs located presynaptically [ 14 ]. Inhibition of neurotransmitter release can be suppressed by the addition of an A 1 R selective inhibitor, such as 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), suggesting that adenosine binding is necessary for the reduction of post synaptic potentials [ 19 ]. It has also been shown that the A 1 R binding of adenosine inhibits NMDA receptor activation [ 20 ].…”

Section: Hypoxia and Synaptic Signalingmentioning

confidence: 99%

The Effects of Hypoxia and Inflammation on Synaptic Signaling in the CNS

Mukandala¹,

Tynan²,

Lanigan³

et al. 2016

Brain Sciences

112

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Normal brain function is highly dependent on oxygen and nutrient supply and when the demand for oxygen exceeds its supply, hypoxia is induced. Acute episodes of hypoxia may cause a depression in synaptic activity in many brain regions, whilst prolonged exposure to hypoxia leads to neuronal cell loss and death. Acute inadequate oxygen supply may cause anaerobic metabolism and increased respiration in an attempt to increase oxygen intake whilst chronic hypoxia may give rise to angiogenesis and erythropoiesis in order to promote oxygen delivery to peripheral tissues. The effects of hypoxia on neuronal tissue are exacerbated by the release of many inflammatory agents from glia and neuronal cells. Cytokines, such as TNF-α, and IL-1β are known to be released during the early stages of hypoxia, causing either local or systemic inflammation, which can result in cell death. Another growing body of evidence suggests that inflammation can result in neuroprotection, such as preconditioning to cerebral ischemia, causing ischemic tolerance. In the following review we discuss the effects of acute and chronic hypoxia and the release of pro-inflammatory cytokines on synaptic transmission and plasticity in the central nervous system. Specifically we discuss the effects of the pro-inflammatory agent TNF-α during a hypoxic event.

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Enzymatic conversion of ATP to adenosine contributes to ATP-induced inhibition of glutamate release in rat medullary dorsal horn neurons

Cited by 15 publications

References 48 publications

Alpl prevents bone ageing sensitivity by specifically regulating senescence and differentiation in mesenchymal stem cells

Alpl prevents bone ageing sensitivity by specifically regulating senescence and differentiation in mesenchymal stem cells

Modulation of excitatory neurotransmission by neuronal/glial signalling molecules: interplay between purinergic and glutamatergic systems

The Effects of Hypoxia and Inflammation on Synaptic Signaling in the CNS

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