{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T22:18:40Z","timestamp":1786745920460,"version":"build-2736575974"},"reference-count":41,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2016,11,29]],"date-time":"2016-11-29T00:00:00Z","timestamp":1480377600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31171108"],"award-info":[{"award-number":["31171108"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2016,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Itch, the unpleasant sensation that evokes a desire to scratch, accompanies numerous skin and nervous system disorders. However, the molecular mechanisms of itch are unclear. Acid\u2010sensing ion channel 3 (<jats:styled-content style=\"fixed-case\">ASIC<\/jats:styled-content>3) is a sensor of acidic and primary inflammatory pain. The whole\u2010cell patch clamp technique was used to determine the effect of chloroquine (<jats:styled-content style=\"fixed-case\">CQ<\/jats:styled-content>) on<jats:styled-content style=\"fixed-case\">ASIC<\/jats:styled-content>s currents in primary sensory neurons or the Chinese hamster ovary cells transfected with rat<jats:styled-content style=\"fixed-case\">ASIC<\/jats:styled-content>1a or<jats:styled-content style=\"fixed-case\">ASIC<\/jats:styled-content>3. Site\u2010directed mutagenesis of plasmid was performed. Scratching behavior was evaluated by measuring the number of bouts during 30\u00a0min after injection.<jats:styled-content style=\"fixed-case\">CQ<\/jats:styled-content>, an anti\u2010malarial drug defined as a histamine\u2010independent pruritogen, selectively enhanced the sustained phase of<jats:styled-content style=\"fixed-case\">ASIC<\/jats:styled-content>3 current in a concentration\u2010dependent manner either in<jats:styled-content style=\"fixed-case\">ASIC<\/jats:styled-content>3\u2010transfected Chinese hamster ovary cells or in primary cultured rat dorsal root ganglion neurons. Further studies revealed that the effect of<jats:styled-content style=\"fixed-case\">CQ<\/jats:styled-content>on<jats:styled-content style=\"fixed-case\">ASIC<\/jats:styled-content>3 channels depends on the newly identified non\u2010proton ligand\u2010sensing domain. Importantly,<jats:styled-content style=\"fixed-case\">CQ<\/jats:styled-content>\u2010evoked scratching behavior was largely alleviated by<jats:styled-content style=\"fixed-case\">APET<\/jats:styled-content>x2, a selective<jats:styled-content style=\"fixed-case\">ASIC<\/jats:styled-content>3 channel blocker. Like<jats:styled-content style=\"fixed-case\">CQ<\/jats:styled-content>, other compounds such as amiloride, 2\u2010guanidine\u20104\u2010methylquinazoline and neuropeptide<jats:styled-content style=\"fixed-case\">FF<\/jats:styled-content>, which have been previously reported to be non\u2010proton ligands that activate<jats:styled-content style=\"fixed-case\">ASIC<\/jats:styled-content>3, undoubtedly evoked the scratching response. In conclusion,<jats:styled-content style=\"fixed-case\">ASIC<\/jats:styled-content>3, a proton\u2010gated ion channel critical for pain sensation, also functions as an essential component of itch transduction.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p><jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc13869-fig-0009-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.13869","type":"journal-article","created":{"date-parts":[[2016,10,22]],"date-time":"2016-10-22T07:53:30Z","timestamp":1477122810000},"page":"1093-1101","source":"Crossref","is-referenced-by-count":11,"title":["Non\u2010proton ligand\u2010sensing domain of acid\u2010sensing ion channel 3 is required for itch sensation"],"prefix":"10.1111","volume":"139","author":[{"given":"Zhen","family":"Lei","sequence":"first","affiliation":[{"name":"Department of Physiology School of Medicine Qilu Hospital Shandong University Jinan Shandong China"},{"name":"Department of Anesthesiology Qilu Hospital Shandong University Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdul","family":"Sami Shaikh","sequence":"additional","affiliation":[{"name":"Institute of Clinical Pharmacology Qilu Hospital of Shandong University Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenshuai","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Physiology School of Medicine Qilu Hospital Shandong University Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Physiology School of Medicine Qilu Hospital Shandong University Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingui","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Qilu Hospital Shandong University Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingxin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Physiology School of Medicine Qilu Hospital Shandong University Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,11,29]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0196-9781(99)00039-X"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)81144-7"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0705754"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10607"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.j.pain.0000460335.49525.17"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0028-3908(01)00107-1"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1253\/circj.CJ-10-0490"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2008.213"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2005.06.031"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2014.12.016"},{"key":"e_1_2_8_12_1","doi-asserted-by":"crossref","first-page":"297","DOI":"10.2340\/0001555559297300","article-title":"Effects of histamine receptor antagonists on histamine\u2010induced responses in human skin","volume":"59","author":"Hagermark O.","year":"1979","journal-title":"Acta Derm. 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