{"id":1205,"date":"2016-04-08T09:49:22","date_gmt":"2016-04-08T00:49:22","guid":{"rendered":"http:\/\/misterx95.myds.me\/?p=1205"},"modified":"2016-04-08T09:49:22","modified_gmt":"2016-04-08T00:49:22","slug":"2016-04-08","status":"publish","type":"post","link":"https:\/\/misterx95.myds.me\/wordpress\/?p=1205","title":{"rendered":"2016.04.08"},"content":{"rendered":"

Impaired Itching Perception in Murine\u00a0Models of Cholestasis Is Supported by\u00a0Dysregulation of GPBAR1 Signaling<\/strong>
\nSabrina Cipriani1\u262f, Barbara Renga2\u262f, Claudio D\u2019Amore2, Michele Simonetti2, Antonio
\nAngelo De Tursi2, Adriana Carino2, Maria Chiara Monti3, Valentina Sepe4,
\nAngela Zampella4, Stefano Fiorucci2*
\n1 Department of Medicine University of Perugia, Perugia, Italy, 2 Department of Surgery and Biomedical
\nSciences, University of Perugia, Perugia, Italy, 3 Department of Pharmacy, University of Salerno, Salerno,
\nItaly, 4 Department of Pharmacy, University of Naples \u201cFederico II\u201d, Naples, Italy<\/p>\n

Abstract<\/strong>
\nBackground & Aims
\nIn cholestatic syndromes, body accumulation of bile acids is thought to cause itching. However,
\nthe mechanisms supporting this effect remain elusive. Recently, GPBAR1 (TGR5) a
\nG-protein coupled receptor has been shown to mediate itching caused by intradermal
\nadministration of DCA and LCA. 6\u03b1-ethyl-3\u03b1, 7\u03b1-dihydroxy-24-nor-5\u03b2-cholan-23-ol
\n(BAR502) is a non-bile acid dual ligand for FXR and GPBAR1.
\nMethods
\nCholestasis was induced in wild type and GPBAR1-\/- mice by administration of \u03b1-naphthylisothiocyanate\u00a0(ANIT) or 17\u03b1-ethynylestradiol.
\nResults.
\nIn na\u00efve mice skin application of DCA, TLCA, 6-ECDCA, oleanolic and betulinic acid
\ninduces a GPBAR1 dependent pruritogenic response that could be desensitized by re-challengingthe mice with the same GPBAR1 agonist. In wild type and GPBAR1-\/- mice cholestasisinduced by ANIT fails to induce spontaneous itching and abrogates scratching
\nbehavior caused by intradermal administration of DCA. In this model, co-treatment with
\nBAR502 increases survival, attenuates serum alkaline phosphatase levels and robustly
\nmodulates the liver expression of canonical FXR target genes including OST\u03b1, BSEP, SHP
\nand MDR1, without inducing pruritus. Betulinic acid, a selective GPBAR1 ligand, failed to
\nrescue wild type and GPBAR1-\/- mice from ANIT cholestasis but did not induced itching. In
\nthe 17\u03b1-ethynylestradiol model BAR502 attenuates cholestasis and reshapes bile acid pool
\nwithout inducing itching.<\/p>\n

Impaired itching perception in murine models of cholestasis is supported by dysregulation of GPBAR1 signalling<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

Impaired Itching Perception in Murine\u00a0Models of Cholestasis Is Supported by\u00a0Dysregulation of GPBAR1 Signaling Sabrina Cipriani1\u262f, Barbara Renga2\u262f, Claudio D\u2019Amore2, Michele Simonetti2, Antonio Angelo De Tursi2, Adriana Carino2, Maria Chiara Monti3, Valentina Sepe4, Angela Zampella4, Stefano Fiorucci2* 1 Department of Medicine University of Perugia, Perugia, Italy, 2 Department of Surgery and Biomedical Sciences, University of Perugia, […]<\/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\/1205"}],"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=1205"}],"version-history":[{"count":3,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/1205\/revisions"}],"predecessor-version":[{"id":1210,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/1205\/revisions\/1210"}],"wp:attachment":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=1205"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=1205"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=1205"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}