{"id":3239,"date":"2024-09-06T10:43:37","date_gmt":"2024-09-06T01:43:37","guid":{"rendered":"https:\/\/misterx95.myds.me\/wordpress\/?p=3239"},"modified":"2024-09-06T10:43:38","modified_gmt":"2024-09-06T01:43:38","slug":"journal-club-2024-09-06","status":"publish","type":"post","link":"https:\/\/misterx95.myds.me\/wordpress\/?p=3239","title":{"rendered":"Journal Club 2024.09.06"},"content":{"rendered":"\n

Nociceptive transient receptor potential ankyrin 1 (TRPA1) in sensory neurons are targets of the antifungal drug econazole<\/p>\n\n\n\n

Kaoru Kasuya1, Kenji Takahashi1,2, Miho Hashimoto2 and Toshio Ohta1,2*<\/p>\n\n\n\n

<\/object>Nociceptive-transient-receptor-potential-ankyrin-1-TRPA1-in-sensory-neurons-are-targets-of-the-antifungal-drug-econazole<\/a>Download<\/a><\/div>\n\n\n\n

Abstract<\/strong><\/p>\n\n\n\n

Background<\/strong> Econazole is a widely used imidazole derivative antifungal for treating skin infections. The molecular<\/p>\n\n\n\n

targets for its frequent adverse effects of skin irritation symptoms, such as pruritus, burning sensation, and pain, have<\/p>\n\n\n\n

not been clarified. Transient receptor potential (TRP) channels, non-selective cation channels, are mainly expressed in<\/p>\n\n\n\n

peripheral sensory neurons and serve as sensors for various irritants.<\/p>\n\n\n\n

Methods<\/strong> We investigated the effect of econazole on TRP channel activation by measuring intracellular calcium<\/p>\n\n\n\n

concentration ([Ca2+]i) through fluorescent ratio imaging in mouse dorsal root ganglion (DRG) neurons isolated from<\/p>\n\n\n\n

wild-type, TRPA1(\u2212\/\u2212) and TRPV1(\u2212\/\u2212) mice, as well as in heterologously TRP channel-expressed cells. A cheek injection<\/p>\n\n\n\n

model was employed to assess econazole-induced itch and pain in vivo.<\/p>\n\n\n\n

Results<\/strong> Econazole evoked an increase in [Ca2+]i, which was abolished by the removal of extracellular Ca2+ in mouse<\/p>\n\n\n\n

DRG neurons. The [Ca2+]i responses to econazole were suppressed by a TRPA1 blocker but not by a TRPV1 blocker.<\/p>\n\n\n\n

Attenuation of the econazole-induced [Ca2+]i responses was observed in the TRPA1(\u2212\/\u2212) mouse DRG neurons but was<\/p>\n\n\n\n

not significant in the TRPV1(\u2212\/\u2212) neurons. Econazole increased the [Ca2+]i in HEK293 cells expressing TRPA1 (TRPA1-<\/p>\n\n\n\n

HEK) but not in those expressing TRPV1, although at higher concentrations, it induced Ca2+ mobilization from<\/p>\n\n\n\n

intracellular stores in untransfected na\u00efve HEK293 cells. Miconazole, which is a structural analog of econazole, also<\/p>\n\n\n\n

increased the [Ca2+]i in mouse DRG neurons and TRPA1-HEK, and its nonspecific action was larger than econazole.<\/p>\n\n\n\n

Fluconazole, a triazole drug failed to activate TRPA1 and TRPV1 in mouse DRG neurons and TRPA1-HEK. Econazole<\/p>\n\n\n\n

induced itch and pain in wild-type mice, with reduced responses in TRPA1(\u2212\/\u2212) mice.<\/p>\n\n\n\n

Conclusions<\/strong> These findings suggested that the imidazole derivatives econazole and miconazole may induce skin<\/p>\n\n\n\n

irritation by activating nociceptive TRPA1 in the sensory neurons. Suppression of TRPA1 activation may mitigate the<\/p>\n\n\n\n

adverse effects of econazole.<\/p>\n\n\n\n

Keywords<\/strong> Antifungal, Heterologous expression, Intracellular Ca2+ concentration, Nociceptor, Sensory neuron,<\/p>\n\n\n\n

Transient receptor potential channel<\/p>\n","protected":false},"excerpt":{"rendered":"

Nociceptive transient receptor potential ankyrin 1 (TRPA1) in sensory neurons are targets of the antifungal drug econazole Kaoru Kasuya1, Kenji Takahashi1,2, Miho Hashimoto2 and Toshio Ohta1,2* Abstract Background Econazole is a widely used imidazole derivative antifungal for treating skin infections. The molecular targets for its frequent adverse effects of skin irritation symptoms, such as pruritus, […]<\/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":[],"_links":{"self":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/3239"}],"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=3239"}],"version-history":[{"count":1,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/3239\/revisions"}],"predecessor-version":[{"id":3241,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/3239\/revisions\/3241"}],"wp:attachment":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=3239"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=3239"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=3239"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}