Interactions of pannexin 1 with NMDA and P2X7 receptors in central nervous system pathologies: Possible role on chronic pain

Bravo, David; Maturana, Carola J.; Pélissier, Teresa; Hernández, Alejandro; Constandil, Luís

doi:10.1016/j.phrs.2015.07.016

Cited by 64 publications

(48 citation statements)

References 101 publications

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“…Furthermore, P2X7R could be activated by ATP released from pre-synaptic neurons, which in turn phosphorylates Pannexin-1 channels by Src-famliy kinases (Bravo et al, 2015). Recently Pannexin-1 channels was also demonstrated to form the large pore of the P2X7R (Pelegrin and Surprenant, 2006; Locovei et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Roles of Pannexin-1 Channels in Inflammatory Response through the TLRs/NF-Kappa B Signaling Pathway Following Experimental Subarachnoid Hemorrhage in Rats

Zhou

et al. 2017

Front. Mol. Neurosci.

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Background: Accumulating evidence suggests that neuroinflammation plays a critical role in early brain injury after subarachnoid hemorrhage (SAH). Pannexin-1 channels, as a member of gap junction proteins located on the plasma membrane, releases ATP, ions, second messengers, neurotransmitters, and molecules up to 1 kD into the extracellular space, when activated. Previous studies identified that the opening of Pannexin-1 channels is essential for cellular migration, apoptosis and especially inflammation, but its effects on inflammatory response in SAH model have not been explored yet.Methods: Adult male Sprague-Dawley rats were divided into six groups: sham group (n = 20), SAH group (n = 20), SAH + LV-Scramble-ShRNA group (n = 20), SAH + LV-ShRNA-Panx1 group (n = 20), SAH + LV-NC group (n = 20), and SAH + LV-Panx1-EGFP group (n = 20). The rat SAH model was induced by injection of 0.3 ml fresh arterial, non-heparinized blood into the prechiasmatic cistern in 20 s. In SAH + LV-ShRNA-Panx1 group and SAH + LV-Panx1-EGFP group, lentivirus was administered via intracerebroventricular injection (i.c.v.) at 72 h before the induction of SAH. The Quantitative real-time polymerase chain reaction, electrophoretic mobility shift assay, enzyme-linked immunosorbent assay, immunofluorescence staining, and western blotting were performed to explore the potential interactive mechanism between Pannexin-1 channels and TLR2/TLR4/NF-κB-mediated signaling pathway. Cognitive and memory changes were investigated by the Morris water maze test.Results: Administration with LV-ShRNA-Panx1 markedly decreased the expression levels of TLR2/4/NF-κB pathway-related agents in the brain cortex and significantly ameliorated neurological cognitive and memory deficits in this SAH model. On the contrary, administration of LV-Panx1-EGFP elevated the expressions of TLR2/4/NF-κB pathway-related agents, which correlated with augmented neuronal apoptosis.Conclusion: Pannexin-1 channels may contribute to inflammatory response and neurobehavioral dysfunction through the TLR2/TLR4/NF-κB-mediated pathway signaling after SAH, suggesting a potential role of Pannexin-1 channels could be a potential therapeutic target for the treatment of SAH.

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Section: Discussionmentioning

confidence: 99%

Roles of Pannexin-1 Channels in Inflammatory Response through the TLRs/NF-Kappa B Signaling Pathway Following Experimental Subarachnoid Hemorrhage in Rats

Zhou

et al. 2017

Front. Mol. Neurosci.

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“…Activation of NMDARs results in a burst of ATP release by synaptic and astrocyte-derived Panx1 and Cx43 HCs, respectively, amplifying depolarization (Kim & Kang, 2011;Prochnow et al, 2012;Thompson et al, 2008). Activity-dependent ATP signaling is facilitated by Panx1 coupling to P2X 7 in membrane complexes (Bravo, Maturana, Pelissier, Hernandez, & Constandil, 2015;Pan, Chou, & Sun, 2015), thereby ensuring that NMDAR activation is augmented by the ensuing purinergic drive.…”

Section: Purinergic Signaling In Epilepsymentioning

confidence: 99%

Connexins and pannexins: At the junction of neuro‐glial homeostasis & disease

Lapato

Tiwari‐Woodruff

2017

J of Neuroscience Research

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In the central nervous system (CNS), connexin and pannexin gap junctions and hemichannels are an integral component of homeostatic neuronal excitability and synaptic plasticity. Neuronal connexin (Cx) gap junctions form electrical synapses across biochemically similar GABAergic networks, allowing rapid and extensive inhibition in response to principle neuron excitation. Glial Cx gap junctions link astrocytes and oligodendrocytes in the pan-glial network that is responsible for removing excitotoxic ions and metabolites. In addition, Cx gap junctions between glia help constrain excessive excitatory activity in neurons and facilitate astrocyte Ca2+ slow wave propagation. Pannexins (Panxs) do not form gap junctions in vivo, but Panx hemichannels participate in autocrine and paracrine gliotransmission alongside connexin hemichannels. ATP and other gliotransmitters released by Cx and Panx hemichannels maintain physiologic glutamatergic tone by strengthening synapses and mitigating aberrant high frequency bursting. Under pathological depolarizing and inflammatory conditions, gap junctions and hemichannels become dysregulated, resulting in aberrant neuronal firing and seizure. In this review, we present known contributions of Cxs and Panxs to physiologic neuronal excitation and explore how disruption of gap junctions and hemichannels lead to aberrant glutamatergic transmission, purinergic signaling, and seizures.

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“…It has also been shown that prolonged stimulation of P2X7R results in forming a large pore, which allows the entry of Ca 2+ into the cytosol and the exit of molecules of up to 900 Da, including IL‐1β (Pelegrin and Surprenant, ). In this process, a functional interaction between P2X7R and pannexin‐1 (Panx1) might be involved (Bravo et al, ). Panx1 channels can be activated by prolonged stimulation of P2X7R through intracellular Ca 2+ and Src‐family kinase (Iglesias et al, ; Bravo et al, ).…”

Section: Microglial P2 Receptors In Neuropathic Painmentioning

confidence: 99%

“…In this process, a functional interaction between P2X7R and pannexin‐1 (Panx1) might be involved (Bravo et al, ). Panx1 channels can be activated by prolonged stimulation of P2X7R through intracellular Ca 2+ and Src‐family kinase (Iglesias et al, ; Bravo et al, ). Panx1 then releases ATP to the extracellular space, which in turn leads to reactivation of the P2X7R.…”

Section: Microglial P2 Receptors In Neuropathic Painmentioning

confidence: 99%

P2 receptors, microglial cytokines and chemokines, and neuropathic pain

Tsuda

2016

J of Neuroscience Research

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Neuropathic pain is a debilitating chronic pain and represents a major clinical challenge. The molecular and cellular mechanisms underlying its development and maintenance are not fully understood but involve abnormal excitability in the dorsal horn of the spinal cord. A growing body of evidence has shown that this aberrant excitability may be a consequence not merely of changes in neurons but rather of multiple alterations in microglia, which are resident macrophages in the central nervous system. This review highlights recent advances in our understanding of the mechanisms that underlie neuropathic pain caused by peripheral nerve injury, with a specific focus on purinergic signaling in spinal cord microglia. This provides convincing evidence for a crucial role for microglial purinergic signaling in the pathogenesis of neuropathic pain, and P2 receptors may be potential therapeutic targets for managing neuropathic pain. © 2016 Wiley Periodicals, Inc.

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Interactions of pannexin 1 with NMDA and P2X7 receptors in central nervous system pathologies: Possible role on chronic pain

Cited by 64 publications

References 101 publications

Roles of Pannexin-1 Channels in Inflammatory Response through the TLRs/NF-Kappa B Signaling Pathway Following Experimental Subarachnoid Hemorrhage in Rats

Roles of Pannexin-1 Channels in Inflammatory Response through the TLRs/NF-Kappa B Signaling Pathway Following Experimental Subarachnoid Hemorrhage in Rats

Connexins and pannexins: At the junction of neuro‐glial homeostasis & disease

P2 receptors, microglial cytokines and chemokines, and neuropathic pain

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