Differential co-localisation of the P2X7 receptor subunit with vesicular glutamate transporters VGLUT1 and VGLUT2 in rat CNS

Atkinson, Lucy; Batten, Trevor; Moores, Thomas; Varoqui, Hélène; Erickson, Jeffrey D.; Deuchars, Jim

doi:10.1016/j.neuroscience.2003.08.065

Cited by 77 publications

(50 citation statements)

References 21 publications

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“…1 A). These Abs have been used in previously published reports examining P2X 7 receptor localization and function in neuronal and nonneuronal tissues (Worthington et al, 1999a,b;Deuchars et al, 2001;Kim et al, 2001;Sluyter et al, 2001;Armstrong et al, 2002;Atkinson et al, 2002Atkinson et al, , 2004Le Feuve et al, 2002;Lundy et al, 2002;Sperlagh et al, 2002;Ishii et al, 2003). We found that Cterm-Ab, but not ectoAb-1 or ectoAb-2, were highly selective for P2X 7 receptor protein when expressed in HEK293 cells and compared with untransfected (Fig.…”

Section: Wild-type Rat and Mouse Brainmentioning

confidence: 56%

“…More recently, protein expression studies revealed similar non-neuronal localizations, but these have also shown immunostaining in many brain neurons, at both presynaptic and postsynaptic densities (Deuchars et al, 2001;Armstrong et al, 2002;Atkinson et al, 2002Atkinson et al, , 2004Lundy et al, 2002;Sperlagh et al, 2002;Ishii et al, 2003;Cavaliere et al, 2004). However, immunostaining patterns in neurons have been inconsistent (Deuchars et al, 2001;Armstrong et al, 2002;Atkinson et al, 2002;Sperlagh et al, 2002;Ishii et al, 2003;Lundy et al, 2003;Atkinson et al, 2004).…”

Section: Introductionmentioning

confidence: 97%

“…We examined most areas of the brain but focused our studies on the hippocampus because this is the region where most of the current evidence for the functional ex-pression of the P2X 7 receptor has been obtained (Deuchars et al, 2001;Armstrong et al, 2002;Lundy et al, 2002;Sperlagh et al, 2002;Atkinson et al, 2004). We performed immunocytochemistry, Western blotting, and immunoprecipitation experiments using three separate Abs directed at different epitopes of the P2X 7 protein and on two sets of P2X 7 receptor knock-out mice generated using different strategies.…”

Section: Introductionmentioning

confidence: 99%

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Reanalysis of P2X₇Receptor Expression in Rodent Brain

Sim¹,

Young²,

Sung³

et al. 2004

J. Neurosci.

241

211

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P2X receptors are cationic-selective ion channels gated by extracellular ATP. There are seven subunits (P2X 1-7 ), the first six of which are expressed throughout the peripheral and central nervous systems. P2X 7 receptors are rapidly upregulated and activated as a result of inflammatory stimuli in immune cells, where they act not only as cationic channels but uniquely couple with rapid release of proinflammatory cytokines, cytoskeletal rearrangements, and apoptosis or necrotic cell death. The P2X 7 receptor has been termed the cytolytic non-neuronal P2X receptor because it had not been detected in neurons until recently when it has been immunolocalized to several brain regions, particularly the hippocampus, and has been suggested to be involved in presynaptic modulation of transmitter release. Because its expression in brain neurons may have substantial functional implications, we have performed detailed immunocytochemical, immunoblot, and immunoprecipitation studies on brain and non-neuronal tissue using all currently available antibodies. We first examined rats, but staining patterns were inconsistent among antibodies; we therefore studied mice for which there are two P2X 7 knock-out mice constructs available, one expressing the LacZ transgene. We found that P2X 7 receptor protein is strongly and reliably detected in the submandibular gland and lung of wild-type mice but not in either of the P2X 7 Ϫ/Ϫ mice. However, we failed to find evidence for P2X 7 receptor protein in hippocampal neurons or their input-output projections. Either the P2X 7 protein in the hippocampus is below the limits of detection by the currently available methods or it is not present.

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Section: Wild-type Rat and Mouse Brainmentioning

confidence: 56%

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Reanalysis of P2X₇Receptor Expression in Rodent Brain

Sim¹,

Young²,

Sung³

et al. 2004

J. Neurosci.

241

211

View full text Add to dashboard Cite

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“…However, P2X 7 is not associated to cell death in other cells, such as cerebellar astrocytes (Delicado et al 2005), suggesting that the heterogeneity observed in P2X 7 -mediated actions can be cell and tissue specific and can depend on differences at P2X 7 receptor expression levels. In this respect, there is plenty of data regarding their presence at presynaptic terminals, which has assigned them a function in the regulation of neurotransmitter release (Armstrong et al 2002;Sperlagh et al 2002;Miras-Portugal et al 2003;Atkinson et al 2004;Ireland et al 2004). In addition, P2X 7 receptor expression in astrocytes seems to play a relevant function in neuron-glia communication (Delicado et al 2005;Duan et al 2003;Suadicani et al 2006).…”

Section: Discussionmentioning

confidence: 99%

P2X7 Nucleotide Receptor is Coupled to GSK-3 Inhibition and Neuroprotection in Cerebellar Granule Neurons

et al. 2009

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In this study we report the coupling of nucleotide receptors to GSK-3 signalling, a relevant survival pathway in cerebellar granule neurons. P2X 7 agonist BzATP induced a 3-4-fold increase in GSK-3 phosphorylation, which is reported to be associated with the catalytic activity inhibition. This effect was dependent on extracellular calcium and PKC, and independent of PI3-K (phosphatidyl-inositol-3-kinase)/Akt, the main survival route of neurotrophins. BzATP also prevented the apoptosis of granule neurons induced by the pharmacological inhibition of the PI3-K signalling. Both effects, BzATPmediated GSK-3 phosphorylation and neuroprotection, were abolished by P2X 7 receptor antagonists, BBG, PPADS and A-438079. We found that BzATP prevented the progressive GSK-3 dephosphorylation and caspase-3 activation occurring under conditions of sustained PI3-K inhibition. These results reveal that P2X 7 receptor activation could provide a relevant survival route alternative to classical neurotrophic factors.

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“…On the other hand, on the basis of our data, we cannot completely exclude that in addition to some P2X 7 -like antigen there are some "true" P2X 7 receptors present on mossy fiber terminals that act exclusively on targets that are not involved in synaptic transmission; however, we consider this very unlikely, because in a former study (Kukley et al, 2001) we used another antibody directed against P2X 7 and detected no labeling of the mossy fiber projection at all (our unpublished observation). Because all studies that reported presynaptic P2X 7 used the same antibody (raised against residues 576 -595 of rat P2X 7 ; Alomone Labs, Chemicon, Temecula, CA), it will be interesting to see whether future studies can confirm the presence of presynaptic P2X 7 at other nerve terminals (Deuchars et al, 2001;Miras-Portugal et al, 2003;Atkinson et al, 2004;Puthussery and Fletcher, 2004).…”

Section: Discussionmentioning

confidence: 99%

Ecto-Nucleotidases and Nucleoside Transporters Mediate Activation of Adenosine Receptors on Hippocampal Mossy Fibers by P2X₇Receptor Agonist 2′-3′-O-(4-Benzoylbenzoyl)-ATP

Kukley

Stausberg²,

Adelmann³

et al. 2004

J. Neurosci.

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The ionotropic and cytolytic P2X 7 receptor is typically found on immune cells, where it is involved in the release of cytokines. Recently, P2X 7 receptors were reported to be localized to presynaptic nerve terminals and to modulate transmitter release. In the present study, we reassessed this unexpected role of P2X 7 receptors at hippocampal mossy fiber-CA3 synapses. In agreement with previous findings, the widely used P2X 7 agonist 2Ј-3Ј-O-(4-benzoylbenzoyl)-adenosine-5Ј-triphosphate (BzATP) clearly depressed field potentials (fEPSPs); however, no evidence for an involvement of P2X 7 receptors could be obtained. First, depression of fEPSPs by BzATP was unchanged in P2X 7 Ϫ/Ϫ mice. Second, experiments using P2X 7 Ϫ/Ϫ mice, immunohistochemistry, and electron microscopy showed that the antigen detected by frequently used P2X 7 antibodies is not compatible with a plasmalemmal P2X 7 receptor. Third, BzATP did not alter Ca 2ϩ levels in synaptic terminals. In contrast, the depression of fEPSPs by BzATP was fully blocked by adenosine (A 1 ) receptor antagonists. Furthermore, the application of BzATP also activated postsynaptic A 1 receptor-coupled K ϩ channels. This effect of BzATP was mimicked by ATP and adenosine and was completely prevented by enzymes specifically degrading adenosine. Activation of A 1 -coupled K ϩ channels by BzATP was dependent on ecto-nucleotidases, extracellular enzymes that convert ATP to adenosine. Moreover, the opening of A 1 -coupled K ϩ channels by BzATP was dependent on nucleoside transporters. Taken together, our results indicate that BzATP is extracellularly catabolized to Bz-adenosine and subsequently hetero-exchanged for intracellular adenosine and then depresses mossy fiber fEPSPs through presynaptic A 1 receptors rather than through P2X 7 receptors. Thus, the present study casts doubts on the neuronal localization of P2X 7 receptors in rodent hippocampus.

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Differential co-localisation of the P2X7 receptor subunit with vesicular glutamate transporters VGLUT1 and VGLUT2 in rat CNS

Cited by 77 publications

References 21 publications

Reanalysis of P2X₇Receptor Expression in Rodent Brain

Reanalysis of P2X₇Receptor Expression in Rodent Brain

P2X7 Nucleotide Receptor is Coupled to GSK-3 Inhibition and Neuroprotection in Cerebellar Granule Neurons

Ecto-Nucleotidases and Nucleoside Transporters Mediate Activation of Adenosine Receptors on Hippocampal Mossy Fibers by P2X₇Receptor Agonist 2′-3′-O-(4-Benzoylbenzoyl)-ATP

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Differential co-localisation of the P2X7 receptor subunit with vesicular glutamate transporters VGLUT1 and VGLUT2 in rat CNS

Cited by 77 publications

References 21 publications

Reanalysis of P2X7Receptor Expression in Rodent Brain

Reanalysis of P2X7Receptor Expression in Rodent Brain

P2X7 Nucleotide Receptor is Coupled to GSK-3 Inhibition and Neuroprotection in Cerebellar Granule Neurons

Ecto-Nucleotidases and Nucleoside Transporters Mediate Activation of Adenosine Receptors on Hippocampal Mossy Fibers by P2X7Receptor Agonist 2′-3′-O-(4-Benzoylbenzoyl)-ATP

Contact Info

Product

Resources

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Reanalysis of P2X₇Receptor Expression in Rodent Brain

Reanalysis of P2X₇Receptor Expression in Rodent Brain

Ecto-Nucleotidases and Nucleoside Transporters Mediate Activation of Adenosine Receptors on Hippocampal Mossy Fibers by P2X₇Receptor Agonist 2′-3′-O-(4-Benzoylbenzoyl)-ATP