{"id":1009,"date":"2015-05-22T10:57:05","date_gmt":"2015-05-22T01:57:05","guid":{"rendered":"http:\/\/misterx95.myds.me\/?p=1009"},"modified":"2015-05-22T10:57:05","modified_gmt":"2015-05-22T01:57:05","slug":"journal-club-2015-5-22","status":"publish","type":"post","link":"https:\/\/misterx95.myds.me\/wordpress\/?p=1009","title":{"rendered":"Journal Club 2015.5.22"},"content":{"rendered":"
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\r\n\t\r\n\t\t\"jid2015183a\"\r\n\t<\/a>\r\n<\/dt>\r\n
\r\n\tFilename<\/strong> : jid2015183a.pdf<\/a> (3 MB)\r\n\t
\r\n\tCaption<\/strong> : \r\n<\/dd>\r\n<\/dl>

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Mechanisms Underlying the Scratching Behavior Induced by the Activation of Proteinase Activated Receptor-4 (PAR-4) in Mice.<\/h1>\n
Patricio ES<\/a>1<\/sup>, Costa R<\/a>2<\/sup>, Figueiredo CP<\/a>2<\/sup>, Gers-Barlag K<\/a>3<\/sup>, Bicca MA<\/a>1<\/sup>, Manjavachi MN<\/a>1<\/sup>, Segat GC<\/a>1<\/sup>, Gentry C<\/a>3<\/sup>, Luiz AP<\/a>1<\/sup>, Fernandes ES<\/a>4<\/sup>, Cunha TM<\/a>5<\/sup>, Bevan S<\/a>3<\/sup>,Calixto JB<\/a>1<\/sup>.<\/div>\n
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Author information<\/span><\/a><\/h3>\n
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Abstract<\/h3>\n
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A role for proteinase-activated receptor-4 (PAR-4) was recently suggested in itch sensation. Here, we investigated the mechanisms underlying the pruriceptive actions of the selective PAR-4 agonist AYPGKF-NH2<\/sub> (AYP) in mice. Dorsal intradermal (i.d.) administration of AYP elicited intense scratching behavior in mice, which was prevented by the selective PAR-4 antagonist (pepducin P4pal-10). PAR-4 was found to be co-expressed in 32% of tryptase-positive skin mast cells and AYP caused a 2-fold increase in mast cell degranulation. However, neither the treatment with cromolyn nor the deficiency of mast cells (WBB6F1-KitW\/Wv<\/sup> mice) were able to affect AYP-induced itch. PAR-4 was also found on gastrin releasing peptide (GRP)-positive neurons (pruriceptive fibers), and AYP-induced itch was reduced by the selective GRP receptor antagonist RC-3095. In addition, AYP evoked calcium influx in \u223c1.5% of cultured DRG neurons also sensitive to TRPV1 (capsaicin) and\/or TRPA1 (AITC) agonists. Importantly, AYP-induced itch was reduced by treatment with either the selective TRPV1 (SB366791), TRPA1 (HC-030031) or NK1 (FK888) receptor antagonists. However, genetic loss of TRPV1, but not of TRPA1, diminished AYP-induced calcium influx in DRG neurons and the scratching behavior in mice. These findings provide evidence that PAR-4 activation by AYP causes pruriceptive itch in mice via a TRPV1\/TRPA1-dependent mechanism.Journal of Investigative Dermatology accepted article preview online, 08 May 2015. doi:10.1038\/jid.2015.183.jid2015183a<\/a><\/p>\n<\/div>\n<\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":"

Mechanisms Underlying the Scratching Behavior Induced by the Activation of Proteinase Activated Receptor-4 (PAR-4) in Mice. Patricio ES1, Costa R2, Figueiredo CP2, Gers-Barlag K3, Bicca MA1, Manjavachi MN1, Segat GC1, Gentry C3, Luiz AP1, Fernandes ES4, Cunha TM5, Bevan S3,Calixto JB1. Author information Abstract A role for proteinase-activated receptor-4 (PAR-4) was recently suggested in itch […]<\/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\/1009"}],"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=1009"}],"version-history":[{"count":1,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/1009\/revisions"}],"predecessor-version":[{"id":1011,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/1009\/revisions\/1011"}],"wp:attachment":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=1009"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=1009"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=1009"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}