{"id":764,"date":"2014-07-01T22:01:10","date_gmt":"2014-07-01T13:01:10","guid":{"rendered":"http:\/\/misterx95.myds.me\/?p=764"},"modified":"2014-07-01T22:01:10","modified_gmt":"2014-07-01T13:01:10","slug":"journal-club-2014-7-1","status":"publish","type":"post","link":"https:\/\/misterx95.myds.me\/wordpress\/?p=764","title":{"rendered":"Journal club 2014-7-1"},"content":{"rendered":"

Sensitisation\u00a0of\u00a0TRPV4\u00a0by\u00a0PAR2\u00a0is\u00a0independent\u00a0of\u00a0intracellular\u00a0calcium signalling\u00a0and can be\u00a0mediated\u00a0by thebiased\u00a0agonist\u00a0neutrophil elastase.<\/h1>\n
Sostegni S<\/a>1,\u00a0Diakov A<\/a>,\u00a0McIntyre P<\/a>,\u00a0Bunnett N<\/a>,\u00a0Korbmacher C<\/a>,\u00a0Haerteis S<\/a>.<\/div>\n
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Author information<\/a><\/h3>\n
<\/div>\n<\/div>\n
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sensitisation of TRPV4 by PAR2 is independent of intracellular calcium signalling and can be mediated by the biased agonist neutrophil elastase<\/a><\/h3>\n

<\/h3>\n

Abstract<\/h3>\n
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Proteolytic activation of protease-activated receptor 2 (PAR2) may represent a major mechanism of regulating the transient receptor potential vanilloid 4 (TRPV4) non-selective cation channel in pathophysiological conditions associated with protease activation (e.g. during inflammation). To provide electrophysiological evidence for PAR2-mediated\u00a0TRPV4\u00a0regulation, we characterised the properties of human\u00a0TRPV4\u00a0heterologously expressed in Xenopus laevis oocytes in the presence and absence of co-expressed human PAR2. In outside-out patches from\u00a0TRPV4\u00a0expressing oocytes, we detected single-channel activity typical for\u00a0TRPV4\u00a0with a single-channel conductance of about 100\u00a0pS for outward and 55\u00a0pS for inward currents. The synthetic\u00a0TRPV4\u00a0activator GSK1016790A stimulated\u00a0TRPV4\u00a0mainly by converting previously silent channels into active channels with an open probability of nearly one. In oocytes co-expressing\u00a0TRPV4\u00a0and PAR2, PAR2\u00a0activation by trypsin or by specific PAR2\u00a0agonist\u00a0SLIGRL-NH2potentiated the GSK1016790A-stimulated\u00a0TRPV4\u00a0whole-cell currents several fold, indicative of channel\u00a0sensitisation. Pre-incubation of oocytes with the\u00a0calcium\u00a0chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N’,N’-tetraacetic acid (BAPTA)-AM did not reduce the stimulatory effect of PAR2\u00a0activation on\u00a0TRPV4, which indicates that the effect is\u00a0independent\u00a0of\u00a0intracellular\u00a0calcium signalling.\u00a0Neutrophil elastase, a\u00a0biased\u00a0agonist\u00a0of PAR2\u00a0that does not induce\u00a0intracellular\u00a0calcium signalling, also caused a PAR2-dependent\u00a0sensitisation\u00a0of\u00a0TRPV4. The Rho-kinase inhibitor Y27362 abolishedelastase-stimulated\u00a0sensitisation\u00a0of\u00a0TRPV4, which indicates that Rho-kinase\u00a0signalling\u00a0plays a critical role in PAR2-mediated\u00a0TRPV4\u00a0sensitisation\u00a0by the\u00a0biased\u00a0agonist\u00a0neutrophil elastase. During acute inflammation,\u00a0neutrophil elastase\u00a0may sensitise\u00a0TRPV4\u00a0by a mechanism involving\u00a0biasedagonism of PAR2\u00a0and activation of Rho-kinase.<\/p>\n<\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":"

Sensitisation\u00a0of\u00a0TRPV4\u00a0by\u00a0PAR2\u00a0is\u00a0independent\u00a0of\u00a0intracellular\u00a0calcium signalling\u00a0and can be\u00a0mediated\u00a0by thebiased\u00a0agonist\u00a0neutrophil elastase. Sostegni S1,\u00a0Diakov A,\u00a0McIntyre P,\u00a0Bunnett N,\u00a0Korbmacher C,\u00a0Haerteis S. Author information sensitisation of TRPV4 by PAR2 is independent of intracellular calcium signalling and can be mediated by the biased agonist neutrophil elastase Abstract Proteolytic activation of protease-activated receptor 2 (PAR2) may represent a major mechanism of regulating the transient receptor potential […]<\/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\/764"}],"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=764"}],"version-history":[{"count":2,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/764\/revisions"}],"predecessor-version":[{"id":766,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/764\/revisions\/766"}],"wp:attachment":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=764"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=764"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=764"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}