{"id":883,"date":"2014-11-17T13:43:28","date_gmt":"2014-11-17T04:43:28","guid":{"rendered":"http:\/\/misterx95.myds.me\/?p=883"},"modified":"2014-11-17T13:43:28","modified_gmt":"2014-11-17T04:43:28","slug":"journal-club-2014-11-17","status":"publish","type":"post","link":"https:\/\/misterx95.myds.me\/wordpress\/?p=883","title":{"rendered":"Journal Club 2014.11.17"},"content":{"rendered":"

Neural peptidase endothelin-converting enzyme 1 regulates endothelin 1-induced pruritus<\/a><\/h1>\n

supplementary neural peptidase<\/a><\/h1>\n

Neural peptidase endothelin-converting enzyme 1 regulates endothelin 1-induced pruritus.<\/h1>\n
Kido-Nakahara M<\/a>,\u00a0Buddenkotte J<\/a>,\u00a0Kempkes C<\/a>,\u00a0Ikoma A<\/a>,\u00a0Cevikbas F<\/a>,\u00a0Akiyama T<\/a>,\u00a0Nunes F<\/a>,\u00a0Seeliger S<\/a>,\u00a0Hasdemir B<\/a>,\u00a0Mess C<\/a>,\u00a0Buhl T<\/a>,\u00a0Sulk M<\/a>,\u00a0M\u00fcller FU<\/a>,\u00a0Metze D<\/a>,Bunnett NW<\/a>,\u00a0Bhargava A<\/a>,\u00a0Carstens E<\/a>,\u00a0Furue M<\/a>,\u00a0Steinhoff M<\/a>.<\/div>\n
\n

Abstract<\/h3>\n
\n

In humans, pruritus (itch) is a common but poorly understood symptom in numerous skin and systemic diseases. Endothelin 1 (ET-1) evokes histamine-independent pruritus in mammals through activation of its cognate G protein-coupled receptor endothelin A receptor (ETAR). Here, we have identified neural endothelin-converting enzyme 1 (ECE-1) as a key regulator of ET-1-induced pruritus and neural signaling of itch. We show here that ETAR, ET-1, and ECE-1 are expressed and colocalize in murine dorsal root ganglia (DRG) neurons and human skin nerves. In murine DRG neurons, ET-1 induced internalization of ETAR within ECE-1-containing endosomes. ECE-1 inhibition slowed ETAR recycling yet prolonged ET-1-induced activation of ERK1\/2, but not p38. In a murine itch model, ET-1-induced scratching behavior was substantially augmented by pharmacological ECE-1 inhibition and abrogated by treatment with an ERK1\/2 inhibitor. Using iontophoresis, we demonstrated that ET-1 is a potent, partially histamine-independent pruritogen in humans. Immunohistochemical evaluation of skin from prurigo nodularis patients confirmed an upregulation of the ET-1\/ETAR\/ECE-1\/ERK1\/2 axis in patients with chronic itch. Together, our data identify the neural peptidase ECE-1 as a negative regulator of itch on sensory nerves by directly regulating ET-1-induced pruritus in humans and mice. Furthermore, these results implicate the ET-1\/ECE-1\/ERK1\/2 pathway as a therapeutic target to treat pruritus in humans.<\/p>\n<\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":"

Neural peptidase endothelin-converting enzyme 1 regulates endothelin 1-induced pruritus supplementary neural peptidase Neural peptidase endothelin-converting enzyme 1 regulates endothelin 1-induced pruritus. Kido-Nakahara M,\u00a0Buddenkotte J,\u00a0Kempkes C,\u00a0Ikoma A,\u00a0Cevikbas F,\u00a0Akiyama T,\u00a0Nunes F,\u00a0Seeliger S,\u00a0Hasdemir B,\u00a0Mess C,\u00a0Buhl T,\u00a0Sulk M,\u00a0M\u00fcller FU,\u00a0Metze D,Bunnett NW,\u00a0Bhargava A,\u00a0Carstens E,\u00a0Furue M,\u00a0Steinhoff M. Abstract In humans, pruritus (itch) is a common but poorly understood symptom in numerous […]<\/p>\n","protected":false},"author":4,"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\/883"}],"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\/4"}],"replies":[{"embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=883"}],"version-history":[{"count":2,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/883\/revisions"}],"predecessor-version":[{"id":887,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/883\/revisions\/887"}],"wp:attachment":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=883"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=883"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=883"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}