{"id":1552,"date":"2017-12-08T09:51:40","date_gmt":"2017-12-08T00:51:40","guid":{"rendered":"http:\/\/misterx95.myds.me\/?p=1552"},"modified":"2017-12-08T09:51:40","modified_gmt":"2017-12-08T00:51:40","slug":"2017-12-08","status":"publish","type":"post","link":"https:\/\/misterx95.myds.me\/wordpress\/?p=1552","title":{"rendered":"2017.12.08"},"content":{"rendered":"

Targeting human Mas-related G protein-coupled receptor X1 to inhibit persistent pain.<\/h1>\n
Li Z<\/a>1<\/sup>,\u00a0Tseng PY<\/a>1<\/sup>,\u00a0Tiwari V<\/a>2<\/sup>,\u00a0Xu Q<\/a>1<\/sup>,\u00a0He SQ<\/a>2<\/sup>,\u00a0Wang Y<\/a>1<\/sup>,\u00a0Zheng Q<\/a>1<\/sup>,\u00a0Han L<\/a>1<\/sup>,\u00a0Wu Z<\/a>3,<\/sup>4<\/sup>,\u00a0Blobaum AL<\/a>5<\/sup>,\u00a0Cui Y<\/a>6<\/sup>,\u00a0Tiwari V<\/a>2<\/sup>,\u00a0Sun S<\/a>1<\/sup>,\u00a0Cheng Y<\/a>1<\/sup>,\u00a0Huang-Lionnet JH<\/a>2<\/sup>,\u00a0Geng Y<\/a>1<\/sup>,\u00a0Xiao B<\/a>6<\/sup>,\u00a0Peng J<\/a>3,<\/sup>4,<\/sup>7<\/sup>,\u00a0Hopkins C<\/a>5<\/sup>,\u00a0Raja SN<\/a>2<\/sup>,\u00a0Guan Y<\/a>8<\/sup>,\u00a0Dong X<\/a>9,<\/sup>10<\/sup>.<\/div>\n
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Abstract<\/h3>\n
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Human Mas-related G protein-coupled receptor X1 (MRGPRX1) is a promising target for pain inhibition, mainly because of its restricted expression in nociceptors within the peripheral nervous system. However, constrained by species differences across\u00a0Mrgprs<\/i>, drug candidates that activate MRGPRX1 do not activate rodent receptors, leaving no responsive animal model to test the effect on pain in vivo. Here, we generated a transgenic mouse line in which we replaced mouse\u00a0Mrgprs<\/i>\u00a0with human\u00a0MrgprX1<\/i>\u00a0This humanized mouse allowed us to characterize an agonist [bovine adrenal medulla 8-22 (BAM8-22)] and a positive allosteric modulator (PAM), ML382, of MRGPRX1. Cellular studies suggested that ML382 enhances the ability of BAM8-22 to inhibit high-voltage-activated Ca2+<\/sup>\u00a0channels and attenuate spinal nociceptive transmission. Importantly, both BAM8-22 and ML382 effectively attenuated evoked, persistent, and spontaneous pain without causing obvious side effects. Notably, ML382 by itself attenuated both evoked pain hypersensitivity and spontaneous pain in\u00a0MrgprX1<\/i>\u00a0mice after nerve injury without acquiring coadministration of an exogenous agonist. Our findings suggest that humanized\u00a0MrgprX1<\/i>\u00a0mice provide a promising preclinical model and that activating MRGPRX1 is an effective way to treat persistent pain.<\/p>\n

KEYWORDS: DRG neurons; GPCR; MrgprX1; pain; positive allosteric modulator<\/h4>\n

Targeting human Mas-related G protein coupled receptor X1 to inhibit persistent pain.<\/a><\/p>\n<\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":"

Targeting human Mas-related G protein-coupled receptor X1 to inhibit persistent pain. Li Z1,\u00a0Tseng PY1,\u00a0Tiwari V2,\u00a0Xu Q1,\u00a0He SQ2,\u00a0Wang Y1,\u00a0Zheng Q1,\u00a0Han L1,\u00a0Wu Z3,4,\u00a0Blobaum AL5,\u00a0Cui Y6,\u00a0Tiwari V2,\u00a0Sun S1,\u00a0Cheng Y1,\u00a0Huang-Lionnet JH2,\u00a0Geng Y1,\u00a0Xiao B6,\u00a0Peng J3,4,7,\u00a0Hopkins C5,\u00a0Raja SN2,\u00a0Guan Y8,\u00a0Dong X9,10. Abstract Human Mas-related G protein-coupled receptor X1 (MRGPRX1) is a promising target for pain inhibition, mainly because of its restricted expression […]<\/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\/1552"}],"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=1552"}],"version-history":[{"count":1,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/1552\/revisions"}],"predecessor-version":[{"id":1554,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/1552\/revisions\/1554"}],"wp:attachment":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=1552"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=1552"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=1552"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}