{"id":114,"date":"2012-09-12T19:24:05","date_gmt":"2012-09-12T10:24:05","guid":{"rendered":"http:\/\/misterx95.myds.me\/?p=114"},"modified":"2012-09-12T19:49:06","modified_gmt":"2012-09-12T10:49:06","slug":"direct-inhibition-of-the-cold-activated-trpm8-ion-channel-by-g%ce%b1q","status":"publish","type":"post","link":"https:\/\/misterx95.myds.me\/wordpress\/?p=114","title":{"rendered":"Journal club 2012-09-13"},"content":{"rendered":"

ncb2529<\/a><\/h1>\n

ncb2529-s1<\/a><\/h1>\n

Direct\u00a0inhibition\u00a0of the\u00a0cold-activated\u00a0TRPM8\u00a0ion\u00a0channel\u00a0by G\u03b1(q).<\/h1>\n
Zhang X<\/a>,\u00a0Mak S<\/a>,\u00a0Li L<\/a>,\u00a0Parra A<\/a>,\u00a0Denlinger B<\/a>,\u00a0Belmonte C<\/a>,\u00a0McNaughton PA<\/a>.<\/div>\n
\n

Source<\/h3>\n

Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, UK.<\/p>\n<\/div>\n

\n

Abstract<\/h3>\n

Activation of the\u00a0TRPM8\u00a0ion\u00a0channel\u00a0in sensory nerve endings produces a sensation of pleasant coolness. Here we show that inflammatory mediators such as bradykinin and histamine inhibit\u00a0TRPM8\u00a0in intact sensory nerves, but do not do so through conventional signalling pathways. The G-protein subunit G\u03b1(q) instead binds to\u00a0TRPM8\u00a0and when activated by a Gq-coupled receptor directly inhibits\u00a0ion\u00a0channel\u00a0activity. Deletion of G\u03b1(q) largely abolished\u00a0inhibition\u00a0of\u00a0TRPM8, and\u00a0inhibition\u00a0was rescued by a G\u03b1(q) chimaera whose ability to activate downstream signalling pathways was completely ablated. Activated G\u03b1(q) protein, but not G\u03b2\u03b3, potently inhibits\u00a0TRPM8\u00a0in excised patches. We conclude that G\u03b1(q) pre-forms a complex with\u00a0TRPM8\u00a0and inhibits activation of\u00a0TRPM8, following activation of G-protein-coupled receptors, by a\u00a0direct\u00a0action. This signalling mechanism may underlie the abnormal cold sensation caused by inflammation.<\/p>\n<\/div>\n

\n
\n
\n
PMID:<\/dt>\n<\/dl>\n

\u00a022750945<\/p>\n

[PubMed – in process]\u00a0PMCID:<\/p>\n

PMC3428855\u00a0[Available on 2013\/2\/1]<\/p>\n<\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":"

ncb2529 ncb2529-s1 Direct\u00a0inhibition\u00a0of the\u00a0cold-activated\u00a0TRPM8\u00a0ion\u00a0channel\u00a0by G\u03b1(q). Zhang X,\u00a0Mak S,\u00a0Li L,\u00a0Parra A,\u00a0Denlinger B,\u00a0Belmonte C,\u00a0McNaughton PA. Source Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, UK. Abstract Activation of the\u00a0TRPM8\u00a0ion\u00a0channel\u00a0in sensory nerve endings produces a sensation of pleasant coolness. Here we show that inflammatory mediators such as bradykinin and histamine inhibit\u00a0TRPM8\u00a0in intact sensory nerves, […]<\/p>\n","protected":false},"author":2,"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":[5],"_links":{"self":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/114"}],"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\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=114"}],"version-history":[{"count":10,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/114\/revisions"}],"predecessor-version":[{"id":127,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/114\/revisions\/127"}],"wp:attachment":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=114"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=114"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=114"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}