{"id":13706,"date":"2024-02-15T11:05:25","date_gmt":"2024-02-15T11:05:25","guid":{"rendered":"https:\/\/www.nanion.de\/?post_type=resource_library&#038;p=13706"},"modified":"2024-02-15T11:05:25","modified_gmt":"2024-02-15T11:05:25","slug":"2015-thyronamine-induces-trpm8-channel-activation-in-human-conjunctival-epithelial-cells","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/zh-hans\/resource_library\/2015-thyronamine-induces-trpm8-channel-activation-in-human-conjunctival-epithelial-cells\/","title":{"rendered":"2015 &#8211; Thyronamine induces TRPM8 channel activation in human conjunctival epithelial cells"},"content":{"rendered":"<p>3-Iodothyronamine (T<sub>1<\/sub>AM), an endogenous thyroid hormone (TH) metabolite, induces numerous responses including a spontaneously reversible body temperature decline. As such an effect is associated in the eye with increases in basal tear flow and thermosensitive transient receptor potential melastatin 8 (TRPM8) channel activation, we determined in human conjunctival epithelial cells (IOBA-NHC) if T<sub>1<\/sub>AM also acts as a cooling agent to directly affect TRPM8 activation at a constant temperature. RT-PCR and quantitative real-time PCR (qPCR) along with immunocytochemistry probed for TRPM8 gene and protein expression whereas functional activity was evaluated by comparing the effects of T<sub>1<\/sub>AM with those of TRPM8 mediators on intracellular Ca<sup>2\u00a0+<\/sup>\u00a0([Ca<sup>2\u00a0+<\/sup>]<sub>i<\/sub>) and whole-cell currents. TRPM8 gene and protein expression was evident and icilin (20\u00a0\u03bcM), a TRPM8 agonist, increased Ca<sup>2\u00a0+<\/sup>\u00a0influx as well as whole-cell currents whereas BCTC (10\u00a0\u03bcM), a TRPM8 antagonist, suppressed these effects. Similarly, either temperature lowering below 23\u00a0\u00b0C or T<sub>1<\/sub>AM (1\u00a0\u03bcM) induced Ca<sup>2\u00a0+<\/sup>\u00a0transients that were blocked by this antagonist. TRPM8 activation by both 1\u00a0\u00b5M T<sub>1<\/sub>AM and 20\u00a0\u03bcM icilin prevented capsaicin (CAP) (20\u00a0\u03bcM) from inducing increases in Ca<sup>2\u00a0+<\/sup>\u00a0influx through TRP vanilloid 1 (TRPV1) activation, whereas BCTC did not block this response. CAP (20\u00a0\u03bcM) induced a 2.5-fold increase in IL-6 release whereas during exposure to 20\u00a0\u03bcM capsazepine this rise was completely blocked. Similarly, T<sub>1<\/sub>AM (1\u00a0\u03bcM) prevented this response. Taken together, T<sub>1<\/sub>AM like icilin is a cooling agent since they both directly elicit TRPM8 activation at a constant temperature. Moreover, there is an inverse association between changes in TRPM8 and TRPV1 activity since these cooling agents blocked both CAP-induced TRPV1 activation and downstream rises in IL-6 release.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[45],"resource_type":[75],"application_areas":[50,76],"therapeutic_areas":[],"target_categories":[338],"target_families":[339],"targets":[122],"resource_keyword":[],"class_list":["post-13706","resource_library","type-resource_library","status-publish","hentry","products_tags-port-a-patch","resource_type-publication","application_areas-ion-channels","application_areas-drug-discovery","target_categories-other-ion-channels","target_families-trp-channels","targets-trpm8"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_library\/13706","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_library"}],"about":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/types\/resource_library"}],"wp:attachment":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/media?parent=13706"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/products_tags?post=13706"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_type?post=13706"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/application_areas?post=13706"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/therapeutic_areas?post=13706"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_categories?post=13706"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_families?post=13706"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/targets?post=13706"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_keyword?post=13706"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}