Trophic effects of purines in neurons and glial cells

Rathbone, Michel P.; Middlemiss, Pamela J.; Gysbers, John W.; Andrew, C.; Herman, Mary; Reed, Juta K.; Ciccarelli, Renata; Iorio, Patrizia Di; Caciagli, Francesco

doi:10.1016/s0301-0082(99)00017-9

Cited by 350 publications

(264 citation statements)

References 277 publications

Supporting

Mentioning

256

Contrasting

Unclassified

Order By: Relevance

“…In fact, the activation of adenosine receptors can modify the primary metabolism of most cell types (see [1]) and this is also true for both neurons and astrocytes [101,102] and in particular for the control of glygogen metabolism [51, 103,104]. However, it still remains to be explored if this modulation of brain metabolism by adenosine receptors is implicated in the neuromodulatory or neuroprotective properties of adenosine or if it might be related with the trophic effects of purines (see [105]). …”

Section: Modulatory Roles Of Adenosinementioning

confidence: 99%

Neuroprotection by adenosine in the brain: From A1 receptor activation to A2A receptor blockade

Cunha

2005

Purinergic Signalling

484

437

View full text Add to dashboard Cite

Adenosine is a neuromodulator that operates via the most abundant inhibitory adenosine A 1 receptors (A 1 Rs) and the less abundant, but widespread, facilitatory A 2A Rs. It is commonly assumed that A 1 Rs play a key role in neuroprotection since they decrease glutamate release and hyperpolarize neurons. In fact, A 1 R activation at the onset of neuronal injury attenuates brain damage, whereas its blockade exacerbates damage in adult animals. However, there is a down-regulation of central A 1 Rs in chronic noxious situations. In contrast, A 2A Rs are up-regulated in noxious brain conditions and their blockade confers robust brain neuroprotection in adult animals. The brain neuroprotective effect of A 2A R antagonists is maintained in chronic noxious brain conditions without observable peripheral effects, thus justifying the interest of A 2A R antagonists as novel protective agents in neurodegenerative diseases such as Parkinson's and Alzheimer's disease, ischemic brain damage and epilepsy. The greater interest of A 2A R blockade compared to A 1 R activation does not mean that A 1 R activation is irrelevant for a neuroprotective strategy. In fact, it is proposed that coupling A 2A R antagonists with strategies aimed at bursting the levels of extracellular adenosine (by inhibiting adenosine kinase) to activate A 1 Rs might constitute the more robust brain neuroprotective strategy based on the adenosine neuromodulatory system. This strategy should be useful in adult animals and especially in the elderly (where brain pathologies are prevalent) but is not valid for fetus or newborns where the impact of adenosine receptors on brain damage is different.Abbreviations: Ab -b-amyloid peptide; A 1 Rs -A 1 receptors; A 2A Rs -A 2A

show abstract

Section: Modulatory Roles Of Adenosinementioning

confidence: 99%

Neuroprotection by adenosine in the brain: From A1 receptor activation to A2A receptor blockade

Cunha

2005

Purinergic Signalling

484

437

View full text Add to dashboard Cite

show abstract

“…However, besides their effect on the proliferation of glial progenitors, several experimental data suggest that nucleotides are involved in the growth of glial cells in the reactive gliosis that occurs when adult nervous tissue is injured [33,34]. In order to investigate if nucleotides were involved in the growth of glial cells over the scratched area of the monolayer retinal cultures, scratched cultures at E8C7 were incubated with 2.5 U/mL of apyrase, an enzyme that hydrolyses nucleoside triphosphates and diphosphates (Fig.…”

Section: Resultsmentioning

confidence: 99%

Involvement of nucleotides in glial growth following scratch injury in avian retinal cell monolayer cultures

Silva

França

Ornelas

et al. 2015

Purinergic Signalling

View full text Add to dashboard Cite

When retinal cell cultures were mechanically scratched, cell growth over the empty area was observed. Only dividing and migrating, 2 M6-positive glial cells were detected. Incubation of cultures with apyrase (APY), suramin, or Reactive Blue 2 (RB-2), but not MRS 2179, significantly attenuated the growth of glial cells, suggesting that nucleotide receptors other than P2Y 1 are involved in the growth of glial cells. UTPγS but not ADPβS antagonized apyrase-induced growth inhibition in scratched cultures, suggesting the participation of UTP-sensitive receptors. No decrease in proliferating cell nuclear antigen (PCNA + ) cells was observed at the border of the scratch in apyrase-treated cultures, suggesting that glial proliferation was not affected. In apyrase-treated cultures, glial cytoplasm protrusions were smaller and unstable. Actin filaments were less organized and alfa-tubulinlabeled microtubules were mainly parallel to scratch. In contrast to control cultures, very few vinculin-labeled adhesion sites could be noticed in these cultures. Increased Akt and ERK phosphorylation was observed in UTP-treated cultures, effect that was inhibited by SRC inhibitor 1 and PI3K blocker LY294002. These inhibitors and the FAK inhibitor PF573228 also decreased glial growth over the scratch, suggesting participation of SRC, PI3K, and FAK in UTP-induced growth of glial cells in scratched cultures. RB-2 decreased dissociated glial cell attachment to fibronectin-coated dishes and migration through transwell membranes, suggesting that nucleotides regulated adhesion and migration of glial cells. In conclusion, mechanical scratch of retinal cell cultures induces growth of glial cells over the empty area through a mechanism that is dependent on activation of UTP-sensitive receptors, SRC, PI3K, and FAK.

show abstract

“…In astrocytes, ATP stimulates the sythesis and release of protein trophic factors, acts in combination with growth factors to stimulate proliferation, and contributes to the process of reactive gliosis, a hypertrophic/hyperplastic reaction which enables the injured brain to restore its functions [38,50] .…”

Section: Discussionmentioning

confidence: 99%

“…The purines/pyrimidines may indeed reach high extracellular levels, despite the strict control exerted by ectonucleotidases which try to maintain their low physiological concentrations. Once in the extracellular environment, purines/pyrimidines generally mediated dual effects: shortterm such as neurotransmission [5] , and long-term such as tropic actions [38] . Besides acting alone as a neurotransmitter, neuromodulator or growth factor, ATP is also often co-released with acetylcholine [39] , noradrenaline [40] and GABA [41] , depending on the specific transmitter receptors of each neuron.…”

Section: Neuroprotective and Neurotoxic Actions Of Extracellular Atpmentioning

confidence: 99%

Therapeutic potential of extracellular ATP and P2 receptors in nervous system diseases

Tu¹,

Wang²

2009

Neurosci. Bull.

View full text Add to dashboard Cite

Extracellular adenosine 5'-triphosphate (ATP) is a key signaling molecule present in the central nervous system (CNS), and now is receiving greater attention due to its role as a messenger in the CNS during different physiological and pathological events. ATP is released into the extracellular space through vesicular exocytosis or from damaged and dying cells. Once in the extracellular environment, ATP binds to the specific receptors termed P2, which mediate ATP effects and are present broadly in both neurons and glial cells. There are P2X, the ligand-gated ionotropic receptors, possessing low affinity for ATP and responsible for fast excitatory neurotransmission, and P2Y, the metabotropic G-protein-coupled receptors, possessing high affinity for ATP. Since massive extracellular release of ATP often occurs after stress, brain ischemia and trauma, the extracellular ATP is considered relating to or involving in the pathological processes of many nervous system diseases. Conversely, the trophic functions have also been extensively described for the extracellular ATP. Therefore, extracellular ATP plays a very complex role in the CNS and its binding to P2 receptors can be related to toxic and/or beneficial effects. In this review, we described the extracellular ATP acting via P2 receptors as a potent therapeutic target for treatment of nervous system diseases.

show abstract

Trophic effects of purines in neurons and glial cells

Cited by 350 publications

References 277 publications

Neuroprotection by adenosine in the brain: From A1 receptor activation to A2A receptor blockade

Neuroprotection by adenosine in the brain: From A1 receptor activation to A2A receptor blockade

Involvement of nucleotides in glial growth following scratch injury in avian retinal cell monolayer cultures

Therapeutic potential of extracellular ATP and P2 receptors in nervous system diseases

Contact Info

Product

Resources

About