Anoctamin 1/TMEM16A in pruritoceptors is essential for Mas-related G protein receptor-dependent itch

Hyesu Kim, Hyungsup Kim, Hawon Cho, Byeongjun Lee, Huan Jun Lu, Kyungmin Kim, Sooyoung Chung, Won Sik Shim, Young Kee Shin, Xinzhong Dong, John N. Wood, Uhtaek Oh

Research output: Contribution to journalArticlepeer-review


Itch is an unpleasant sensation that evokes a desire to scratch. Pathologic conditions such as allergy or atopic dermatitis produce severe itching sensation. Mas-related G protein receptors (Mrgprs) are receptors for many endogenous pruritogens. However, signaling pathways downstream to these receptors in dorsal root ganglion (DRG) neurons are not yet understood. We found that anoctamin 1 (ANO1), a Ca2+-activated chloride channel, is a transduction channel mediating Mrgpr-dependent itch signals. Genetic ablation of Ano1 in DRG neurons displayed a significant reduction in scratching behaviors in response to acute and chronic Mrgpr-dependent itch models and the epidermal hyperplasia induced by dry skin. In vivo Ca2+imaging and electrophysiological recording revealed that chloroquine and other agonists of Mrgprs excited DRG neurons via ANO1. More importantly, the overexpression of Ano1 in DRG neurons of Ano1-deficient mice rescued the impaired itching observed in Ano1-deficient mice. These results demonstrate that ANO1 mediates the Mrgpr-dependent itch signaling in pruriceptors and provides clues to treating pathologic itch syndromes.

Original languageEnglish (US)
Pages (from-to)2172-2184
Number of pages13
Issue number11
StatePublished - Nov 1 2022


  • Anoctamin 1
  • Bilirubin
  • Chloroquine
  • Itch
  • Mrgprs
  • Pruriceptors

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology
  • Anesthesiology and Pain Medicine


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