Kim, Hyesu Kim, Hyungsup Cho, Hawon Lee, Byeongjun Lu, Huan-Jun Kim, Kyungmin Chung, Sooyoung Shim, Won-Sik Shin, Young Kee Dong, Xinzhong Wood, John N. Oh, Uhtaek 2024-01-19T11:00:22Z 2024-01-19T11:00:22Z 2022-11-04 2022-11 0304-3959 https://pubs.kist.re.kr/handle/201004/114409 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. English Elsevier BV Anoctamin 1/TMEM16A in pruritoceptors is essential for Mas-related G protein receptor-dependent itch Article 10.1097/j.pain.0000000000002611 1 Pain, v.163, no.11, pp.2172 - 2184 Pain 163 11 2172 2184 N scie scopus 000868828900014 Anesthesiology Clinical Neurology Neurosciences Anesthesiology Neurosciences & Neurology Article BEHAVIORAL-RESPONSES SENSORY NEURONS MOUSE MODEL DRY SKIN ACTIVATION HISTAMINE PAIN MECHANISMS PRURITUS PEPTIDE Anoctamin 1 Pruriceptors Itch Mrgprs Bilirubin Chloroquine