{"title":"Anoctamin 1,疼痛和瘙痒的多模式参与者","authors":"Hyungsup Kim , Won-Sik Shim , Uhtaek Oh","doi":"10.1016/j.ceca.2024.102924","DOIUrl":null,"url":null,"abstract":"<div><p>Anoctamin 1 (ANO1/TMEM16A) encodes a Ca<sup>2+</sup>-activated Cl<sup>-</sup> channel. Among ANO1′s many physiological functions, it plays a significant role in mediating nociception and itch. ANO1 is activated by intracellular Ca<sup>2+</sup> and depolarization. Additionally, ANO1 is activated by heat above 44 °C, suggesting heat as another activation stimulus. ANO1 is highly expressed in nociceptors, indicating a role in nociception. Conditional Ano1 ablation in dorsal root ganglion (DRG) neurons results in a reduction in acute thermal pain, as well as thermal and mechanical allodynia or hyperalgesia evoked by inflammation or nerve injury. Pharmacological interventions also lead to a reduction in nocifensive behaviors. ANO1 is functionally linked to the bradykinin receptor and TRPV1. Bradykinin stimulates ANO1 via IP3-mediated Ca<sup>2+</sup> release from intracellular stores, whereas TRPV1 stimulates ANO1 via a combination of Ca<sup>2+</sup> influx and release. Nerve injury causes upregulation of ANO1 expression in DRG neurons, which is blocked by ANO1 antagonists. Due to its role in nociception, strong and specific ANO1 antagonists have been developed. ANO1 is also expressed in pruritoceptors, mediating Mas-related G protein-coupled receptors (Mrgprs)-dependent itch. The activation of ANO1 leads to chloride efflux and depolarization due to high intracellular chloride concentrations, causing pain and itch. Thus, ANO1 could be a potential target for the development of new drugs treating pain and itch.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":null,"pages":null},"PeriodicalIF":4.3000,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0143416024000824/pdfft?md5=423b075f13875d438ee3a3b93e33c9dc&pid=1-s2.0-S0143416024000824-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Anoctamin 1, a multi-modal player in pain and itch\",\"authors\":\"Hyungsup Kim , Won-Sik Shim , Uhtaek Oh\",\"doi\":\"10.1016/j.ceca.2024.102924\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Anoctamin 1 (ANO1/TMEM16A) encodes a Ca<sup>2+</sup>-activated Cl<sup>-</sup> channel. Among ANO1′s many physiological functions, it plays a significant role in mediating nociception and itch. ANO1 is activated by intracellular Ca<sup>2+</sup> and depolarization. Additionally, ANO1 is activated by heat above 44 °C, suggesting heat as another activation stimulus. ANO1 is highly expressed in nociceptors, indicating a role in nociception. Conditional Ano1 ablation in dorsal root ganglion (DRG) neurons results in a reduction in acute thermal pain, as well as thermal and mechanical allodynia or hyperalgesia evoked by inflammation or nerve injury. Pharmacological interventions also lead to a reduction in nocifensive behaviors. ANO1 is functionally linked to the bradykinin receptor and TRPV1. Bradykinin stimulates ANO1 via IP3-mediated Ca<sup>2+</sup> release from intracellular stores, whereas TRPV1 stimulates ANO1 via a combination of Ca<sup>2+</sup> influx and release. Nerve injury causes upregulation of ANO1 expression in DRG neurons, which is blocked by ANO1 antagonists. Due to its role in nociception, strong and specific ANO1 antagonists have been developed. ANO1 is also expressed in pruritoceptors, mediating Mas-related G protein-coupled receptors (Mrgprs)-dependent itch. The activation of ANO1 leads to chloride efflux and depolarization due to high intracellular chloride concentrations, causing pain and itch. 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引用次数: 0
摘要
Anoctamin 1(ANO1/TMEM16A)编码一种钙激活的 Cl 通道。在 ANO1 的多种生理功能中,它在介导痛觉和瘙痒方面发挥着重要作用。ANO1 由细胞内 Ca 和去极化激活。此外,44 °C以上的高温也会激活ANO1,这表明高温是另一种激活刺激。ANO1 在痛觉感受器中高度表达,表明其在痛觉中发挥作用。对背根神经节(DRG)神经元进行条件性 Ano1 消融可减轻急性热痛以及炎症或神经损伤诱发的热和机械异感或痛觉减退。药物干预也会导致痛觉强化行为的减少。ANO1 在功能上与缓激肽受体和 TRPV1 有关。缓激肽通过 IP3 介导的 Ca 从细胞内储存释放来刺激 ANO1,而 TRPV1 则通过 Ca 流入和释放的组合来刺激 ANO1。神经损伤会导致 DRG 神经元中 ANO1 的表达上调,而 ANO1 拮抗剂会阻断 ANO1 的表达。由于 ANO1 在痛觉中的作用,人们开发出了强效特异性 ANO1 拮抗剂。ANO1 也在瘙痒感受器中表达,介导 Mas 相关 G 蛋白偶联受体(Mrgprs)依赖性瘙痒。ANO1 激活后会导致氯离子外流,细胞内氯离子浓度过高导致去极化,从而引起疼痛和瘙痒。因此,ANO1 可能是开发治疗疼痛和瘙痒新药的潜在靶点。
Anoctamin 1, a multi-modal player in pain and itch
Anoctamin 1 (ANO1/TMEM16A) encodes a Ca2+-activated Cl- channel. Among ANO1′s many physiological functions, it plays a significant role in mediating nociception and itch. ANO1 is activated by intracellular Ca2+ and depolarization. Additionally, ANO1 is activated by heat above 44 °C, suggesting heat as another activation stimulus. ANO1 is highly expressed in nociceptors, indicating a role in nociception. Conditional Ano1 ablation in dorsal root ganglion (DRG) neurons results in a reduction in acute thermal pain, as well as thermal and mechanical allodynia or hyperalgesia evoked by inflammation or nerve injury. Pharmacological interventions also lead to a reduction in nocifensive behaviors. ANO1 is functionally linked to the bradykinin receptor and TRPV1. Bradykinin stimulates ANO1 via IP3-mediated Ca2+ release from intracellular stores, whereas TRPV1 stimulates ANO1 via a combination of Ca2+ influx and release. Nerve injury causes upregulation of ANO1 expression in DRG neurons, which is blocked by ANO1 antagonists. Due to its role in nociception, strong and specific ANO1 antagonists have been developed. ANO1 is also expressed in pruritoceptors, mediating Mas-related G protein-coupled receptors (Mrgprs)-dependent itch. The activation of ANO1 leads to chloride efflux and depolarization due to high intracellular chloride concentrations, causing pain and itch. Thus, ANO1 could be a potential target for the development of new drugs treating pain and itch.
期刊介绍:
Cell Calcium covers the field of calcium metabolism and signalling in living systems, from aspects including inorganic chemistry, physiology, molecular biology and pathology. Topic themes include:
Roles of calcium in regulating cellular events such as apoptosis, necrosis and organelle remodelling
Influence of calcium regulation in affecting health and disease outcomes