Kim, Hyungsup Shim, Won-Sik Oh, Uhtaek 2024-07-18T06:00:06Z 2024-07-18T06:00:06Z 2024-07-18 2024-11 0143-4160 https://pubs.kist.re.kr/handle/201004/150258 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 degrees 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 proteincoupled 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. English ELSEVIER SCI LTD Anoctamin 1, a multi-modal player in pain and itch Article 10.1016/j.ceca.2024.102924 1 Cell Calcium, v.123 Cell Calcium 123 Y scie scopus 001264939000001 2-s2.0-85197313265 Cell Biology Cell Biology Article ACTIVATED CHLORIDE CHANNEL RAT SENSORY NEURONS NEUROPATHIC PAIN DORSAL-ROOT MUCIN SECRETION SODIUM-CHANNELS BRADYKININ EXPRESSION TMEM16A TRPV1 Anoctamin 1 TMEM16A Nociceptor Pain Itch TRPV1 Mrgpr Neuropathic pain DRG neuron