{"id":1193,"date":"2016-03-18T10:08:24","date_gmt":"2016-03-18T01:08:24","guid":{"rendered":"http:\/\/misterx95.myds.me\/?p=1193"},"modified":"2016-03-18T10:08:24","modified_gmt":"2016-03-18T01:08:24","slug":"2016-03-18","status":"publish","type":"post","link":"https:\/\/misterx95.myds.me\/wordpress\/?p=1193","title":{"rendered":"2016.03.18"},"content":{"rendered":"

Eact, a small molecule activator of TMEM16A,\u00a0activates TRPV1 and elicits pain- and itch- related\u00a0behaviours<\/p>\n

Shenbin Liu1,2,*, Jing Feng1,*, Jialie Luo1, Pu Yang1, Thomas J Brett3 and Hongzhen Hu1<\/p>\n

BACKGROUND AND PURPOSE<\/p>\n

TMEM16A, also known as anoctamin 1 channel, is a member of the Ca2+-activated chloride channels family and serves as a heat\u00a0sensor in the primary nociceptors. Eact is a recently discovered small molecule activator of the TMEM16A channel. Here, we asked\u00a0if Eact produces pain- and itch-related responses in vivo and investigated the cellular and molecular basis of Eact-elicited responses\u00a0in dorsal root ganglia (DRG) neurons.<\/span><\/p>\n

EXPERIMENTAL APPROACH
\nWe employed behavioural testing combined with pharmacological inhibition and genetic ablation approaches to identify\u00a0transient receptor potential vanilloid 1 (TRPV1) as the prominent mediator for Eact-evoked itch- or pain-related responses. We\u00a0investigated the effects of Eact on TRPV1 and TMEM16A channels expressed in HEK293T cells and in DRG neurons isolated from\u00a0wild type and Trpv1\/ mice using Ca2+ imaging and patch-clamp recordings. We also used site-directed mutagenesis to determine\u00a0the molecular basis of Eact activation of TRPV1.<\/p>\n

KEY RESULTS
\nAdministration of Eact elicited both itch- and pain-related behaviours. Unexpectedly, the Eact-elicited behavioural responses were\u00a0dependent on the function of TRPV1, as shown by pharmacological inhibition and genetic ablation studies. Eact activated\u00a0membrane currents and increased intracellular free Ca2+ in both TRPV1-expressing HEK293T cells and isolated DRG neurons in a\u00a0TRPV1-dependent manner. Eact activation of the TRPV1 channel was severely attenuated by mutations disrupting the capsaicin binding\u00a0sites.<\/p>\n

CONCLUSIONS AND IMPLICATIONS
\nOur results suggest that Eact activates primary sensory nociceptors and produces both pain and itch responses mainly through\u00a0direct activation of TRPV1 channels.<\/p>\n

 <\/p>\n

Eact, a small molecule activator of TMEM16A, activates TRPV1 and elicits pain- and itch- related behaviours<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

Eact, a small molecule activator of TMEM16A,\u00a0activates TRPV1 and elicits pain- and itch- related\u00a0behaviours Shenbin Liu1,2,*, Jing Feng1,*, Jialie Luo1, Pu Yang1, Thomas J Brett3 and Hongzhen Hu1 BACKGROUND AND PURPOSE TMEM16A, also known as anoctamin 1 channel, is a member of the Ca2+-activated chloride channels family and serves as a heat\u00a0sensor in the primary […]<\/p>\n","protected":false},"author":7,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}}},"categories":[1],"tags":[],"_links":{"self":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/1193"}],"collection":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/users\/7"}],"replies":[{"embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=1193"}],"version-history":[{"count":3,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/1193\/revisions"}],"predecessor-version":[{"id":1198,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/1193\/revisions\/1198"}],"wp:attachment":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=1193"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=1193"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=1193"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}