Kim, Hyesu;
Kim, Hyungsup;
Cho, Hawon;
Lee, Byeongjun;
Lu, Huan-Jun;
Kim, Kyungmin;
Chung, Sooyoung;
... Oh, Uhtaek; + view all
(2022)
Anoctamin 1/TMEM16A in pruritoceptors is essential for Mas-related G protein receptor-dependent itch.
Pain
, 163
(11)
pp. 2172-2184.
10.1097/j.pain.0000000000002611.
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Abstract
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 Mrgprs-dependent itch signals. Genetic ablation of Ano1 in DRG neurons displayed a significant reduction in scratching behaviors in response to acute and chronic Mrgprs-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 Mrgpr receptors 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 Mrgprs-dependent itch signaling in pruriceptors and provides clues to treating pathologic itch syndromes.
| Type: | Article |
|---|---|
| Title: | Anoctamin 1/TMEM16A in pruritoceptors is essential for Mas-related G protein receptor-dependent itch |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1097/j.pain.0000000000002611 |
| Publisher version: | http://doi.org/10.1097/j.pain.0000000000002611 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Anoctamin 1; Pruriceptors; itch; Mrgprs; Bilirubin; Chloroquine |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Wolfson Inst for Biomedical Research UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10145685 |
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