{"history":[],"article":{"id":"891ca440-939f-49f7-a5f6-ee669a7b9e02","title":"P2RX7","slug":"p2rx7","content":":::summary\n:::\n\n# \n**P2X purinoceptor 7** is a [protein](https://bliptext.com/articles/protein) that in humans is encoded by the P2RX7 [gene](https://bliptext.com/articles/gene).\nThe product of this gene belongs to the family of [purinoceptors](https://bliptext.com/articles/purinergic-receptor) for [ATP](https://bliptext.com/articles/adenosine-triphosphate).\nMultiple alternatively spliced variants which would encode different isoforms have been identified although some fit [nonsense-mediated decay](https://bliptext.com/articles/nonsense-mediated-decay) criteria.\nThe receptor is found in the central and peripheral nervous systems, in [microglia](https://bliptext.com/articles/microglia), in [macrophages](https://bliptext.com/articles/macrophages), in uterine [endometrium](https://bliptext.com/articles/endometrium), and in the [retina](https://bliptext.com/articles/retina).\nThe P2X₇ receptor also serves as a [pattern recognition receptor](https://bliptext.com/articles/pattern-recognition-receptor) for extracellular ATP-mediated [apoptotic cell death](https://bliptext.com/articles/apoptosis), regulation of receptor trafficking, [mast cell](https://bliptext.com/articles/mast-cell) [degranulation](https://bliptext.com/articles/degranulation), and [inflammation](https://bliptext.com/articles/inflammation).\nRegarding inflammation, P2X7 receptor induces the NLRP3 [inflammasome](https://bliptext.com/articles/inflammasome) in myeloid cells and leads to [interleukin-1beta](https://bliptext.com/articles/interleukin-1-beta) release.\n\n# Structure and kinetics\nThe P2X₇ subunits can form [homomeric](https://bliptext.com/articles/homomeric) receptors only with a typical [P2X receptor](https://bliptext.com/articles/p2x-purinoreceptor) structure.\nThe P2X₇ receptor is a [ligand-gated cation channel](https://bliptext.com/articles/ligand-gated-ion-channel) that opens in response to ATP binding and leads to cell [depolarization](https://bliptext.com/articles/depolarization).\nThe P2X₇ receptor requires higher levels of ATP than other P2X receptors; however, the response can be potentiated by reducing the concentration of divalent cations such as [calcium](https://bliptext.com/articles/calcium) or [magnesium](https://bliptext.com/articles/magnesium).\nContinued binding leads to increased permeability to N-methyl- D -glucamine (NMDG+).\nP2X₇ receptors do not become [desensitized](https://bliptext.com/articles/desensitization-medicine) readily and continued signaling leads to the aforementioned increased permeability and an increase in current amplitude.\n\n# Pharmacology\n\n## Agonists\n\n## Antagonists\n\n# Receptor trafficking\nIn [microglia](https://bliptext.com/articles/microglia), P2X₇ receptors are found mostly on the cell surface.\nConserved [cysteine](https://bliptext.com/articles/cysteine) residues located in the [carboxyl](https://bliptext.com/articles/carboxyl) terminus seem to be important for receptor trafficking to the cell membrane.\nThese receptors are upregulated in response to peripheral nerve injury.\nIn melanocytic cells P2X7 gene expression may be regulated by [MITF](https://bliptext.com/articles/microphthalmia-associated-transcription-factor).\n\n# Recruitment of pannexin\nActivation of the P2X7 receptor by [ATP](https://bliptext.com/articles/adenosine-triphosphate) leads to recruitment of [pannexin](https://bliptext.com/articles/pannexin) pores which allow small molecules such as [ATP](https://bliptext.com/articles/adenosine-triphosphate) to leak out of cells.\nThis allows further activation of [purinergic receptors](https://bliptext.com/articles/purinergic-receptors) and physiological responses such a spreading cytoplasmic [waves of calcium](https://bliptext.com/articles/astrocyte).\nMoreover, this could be responsible for ATP-dependent lysis of [macrophages](https://bliptext.com/articles/macrophage) through the formation of membrane pores permeable to larger molecules.\n\n# Clinical significance\n\n## Inflammation\nOn [T cells](https://bliptext.com/articles/t-cell) activation of P2X₇ receptors can activate the [T cells](https://bliptext.com/articles/t-cell) or cause T cell differentiation, can affect T cell migration or (at high extracellular levels of ATP and/or NAD+) can induce cell death.\nThe [CD38](https://bliptext.com/articles/cd38) enzyme on [B lymphocytes](https://bliptext.com/articles/b-cell) and [macrophages](https://bliptext.com/articles/macrophage) reduces extracellular NAD+, promoting the survival of T cells.\n\n## Neuropathic pain\n[Microglial](https://bliptext.com/articles/microglia) P2X₇ receptors are thought to be involved in [neuropathic pain](https://bliptext.com/articles/neuropathic-pain) because blockade or deletion of P2X₇ receptors results in decreased responses to pain, as demonstrated [in vivo](https://bliptext.com/articles/in-vivo).\nMoreover, P2X₇ receptor signaling increases the release of proinflammatory molecules such as [IL-1β](https://bliptext.com/articles/il1b), [IL-6](https://bliptext.com/articles/interleukin-6), and [TNF-α](https://bliptext.com/articles/tumor-necrosis-factor-alpha).\nIn addition, P2X₇ receptors have been linked to increases in proinflammatory [cytokines](https://bliptext.com/articles/cytokine) such as [CXCL2](https://bliptext.com/articles/cxcl2) and [CCL3](https://bliptext.com/articles/ccl3).\nP2X₇ receptors are also linked to [P2X₄](https://bliptext.com/articles/p2rx4) receptors, which are also associated with neuropathic pain mediated by microglia.\n\n## Osteoporosis\nMutations in this gene have been associated to low lumbar spine bone mineral density and accelerated bone loss in post-menopausal women.\n\n## Diabetes\nThe ATP/P2X7R pathway may trigger T-cell attacks on the pancreas, rendering it unable to produce insulin.\nThis autoimmune response may be an early mechanism by which the onset of diabetes is caused.\n\n# Research\n\n## Possible link to hepatic fibrosis\nOne study in mice showed that blockade of P2X7 receptors attenuates onset of liver fibrosis.","current_revision":null,"created_by":"kACnuQmH5k9Nr5VNVEpVeg7XpvUmMctD","created_at":"2025-01-26T10:14:18.983Z","updated_at":"2025-01-26T10:14:18.983Z","search_vector":"'p2rx7':1","search_content":" \n \n\n# \n**P2X purinoceptor 7** is a [protein](https://bliptext.com/articles/protein) that in humans is encoded by the P2RX7 [gene](https://bliptext.com/articles/gene).\nThe product of this gene belongs to the family of [purinoceptors](https://bliptext.com/articles/purinergic-receptor) for [ATP](https://bliptext.com/articles/adenosine-triphosphate).\nMultiple alternatively spliced variants which would encode different isoforms have been identified although some fit [nonsense-mediated decay](https://bliptext.com/articles/nonsense-mediated-decay) criteria.\nThe receptor is found in the central and peripheral nervous systems, in [microglia](https://bliptext.com/articles/microglia), in [macrophages](https://bliptext.com/articles/macrophages), in uterine [endometrium](https://bliptext.com/articles/endometrium), and in the [retina](https://bliptext.com/articles/retina).\nThe P2X 7 receptor also serves as a [pattern recognition receptor](https://bliptext.com/articles/pattern-recognition-receptor) for extracellular ATP-mediated [apoptotic cell death](https://bliptext.com/articles/apoptosis), regulation of receptor trafficking, [mast cell](https://bliptext.com/articles/mast-cell) [degranulation](https://bliptext.com/articles/degranulation), and [inflammation](https://bliptext.com/articles/inflammation).\nRegarding inflammation, P2X7 receptor induces the NLRP3 [inflammasome](https://bliptext.com/articles/inflammasome) in myeloid cells and leads to [interleukin-1beta](https://bliptext.com/articles/interleukin-1-beta) release.\n\n# Structure and kinetics\nThe P2X 7 subunits can form [homomeric](https://bliptext.com/articles/homomeric) receptors only with a typical [P2X receptor](https://bliptext.com/articles/p2x-purinoreceptor) structure.\nThe P2X 7 receptor is a [ligand-gated cation channel](https://bliptext.com/articles/ligand-gated-ion-channel) that opens in response to ATP binding and leads to cell [depolarization](https://bliptext.com/articles/depolarization).\nThe P2X 7 receptor requires higher levels of ATP than other P2X receptors; however, the response can be potentiated by reducing the concentration of divalent cations such as [calcium](https://bliptext.com/articles/calcium) or [magnesium](https://bliptext.com/articles/magnesium).\nContinued binding leads to increased permeability to N-methyl- D -glucamine (NMDG+).\nP2X 7 receptors do not become [desensitized](https://bliptext.com/articles/desensitization-medicine) readily and continued signaling leads to the aforementioned increased permeability and an increase in current amplitude.\n\n# Pharmacology\n\n## Agonists\n\n## Antagonists\n\n# Receptor trafficking\nIn [microglia](https://bliptext.com/articles/microglia), P2X 7 receptors are found mostly on the cell surface.\nConserved [cysteine](https://bliptext.com/articles/cysteine) residues located in the [carboxyl](https://bliptext.com/articles/carboxyl) terminus seem to be important for receptor trafficking to the cell membrane.\nThese receptors are upregulated in response to peripheral nerve injury.\nIn melanocytic cells P2X7 gene expression may be regulated by [MITF](https://bliptext.com/articles/microphthalmia-associated-transcription-factor).\n\n# Recruitment of pannexin\nActivation of the P2X7 receptor by [ATP](https://bliptext.com/articles/adenosine-triphosphate) leads to recruitment of [pannexin](https://bliptext.com/articles/pannexin) pores which allow small molecules such as [ATP](https://bliptext.com/articles/adenosine-triphosphate) to leak out of cells.\nThis allows further activation of [purinergic receptors](https://bliptext.com/articles/purinergic-receptors) and physiological responses such a spreading cytoplasmic [waves of calcium](https://bliptext.com/articles/astrocyte).\nMoreover, this could be responsible for ATP-dependent lysis of [macrophages](https://bliptext.com/articles/macrophage) through the formation of membrane pores permeable to larger molecules.\n\n# Clinical significance\n\n## Inflammation\nOn [T cells](https://bliptext.com/articles/t-cell) activation of P2X 7 receptors can activate the [T cells](https://bliptext.com/articles/t-cell) or cause T cell differentiation, can affect T cell migration or (at high extracellular levels of ATP and/or NAD+) can induce cell death.\nThe [CD38](https://bliptext.com/articles/cd38) enzyme on [B lymphocytes](https://bliptext.com/articles/b-cell) and [macrophages](https://bliptext.com/articles/macrophage) reduces extracellular NAD+, promoting the survival of T cells.\n\n## Neuropathic pain\n[Microglial](https://bliptext.com/articles/microglia) P2X 7 receptors are thought to be involved in [neuropathic pain](https://bliptext.com/articles/neuropathic-pain) because blockade or deletion of P2X 7 receptors results in decreased responses to pain, as demonstrated [in vivo](https://bliptext.com/articles/in-vivo).\nMoreover, P2X 7 receptor signaling increases the release of proinflammatory molecules such as [IL-1β](https://bliptext.com/articles/il1b), [IL-6](https://bliptext.com/articles/interleukin-6), and [TNF-α](https://bliptext.com/articles/tumor-necrosis-factor-alpha).\nIn addition, P2X 7 receptors have been linked to increases in proinflammatory [cytokines](https://bliptext.com/articles/cytokine) such as [CXCL2](https://bliptext.com/articles/cxcl2) and [CCL3](https://bliptext.com/articles/ccl3).\nP2X 7 receptors are also linked to [P2X 4 ](https://bliptext.com/articles/p2rx4) receptors, which are also associated with neuropathic pain mediated by microglia.\n\n## Osteoporosis\nMutations in this gene have been associated to low lumbar spine bone mineral density and accelerated bone loss in post-menopausal women.\n\n## Diabetes\nThe ATP/P2X7R pathway may trigger T-cell attacks on the pancreas, rendering it unable to produce insulin.\nThis autoimmune response may be an early mechanism by which the onset of diabetes is caused.\n\n# Research\n\n## Possible link to hepatic fibrosis\nOne study in mice showed that blockade of P2X7 receptors attenuates onset of liver fibrosis.","revisionCount":0},"hasMore":false,"nextCursor":null}

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