{"id":6280,"date":"2023-02-17T07:03:19","date_gmt":"2023-02-17T07:03:19","guid":{"rendered":"https:\/\/beta.nanion.de\/resource_library\/2018-trpm8-activation-via-3-iodothyronamine-blunts-vegf-induced-transactivation-of-trpv1-in-human-uveal-melanoma-cells\/"},"modified":"2023-02-17T07:03:19","modified_gmt":"2023-02-17T07:03:19","slug":"2018-trpm8-activation-via-3-iodothyronamine-blunts-vegf-induced-transactivation-of-trpv1-in-human-uveal-melanoma-cells","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/ja\/resource_library\/2018-trpm8-activation-via-3-iodothyronamine-blunts-vegf-induced-transactivation-of-trpv1-in-human-uveal-melanoma-cells\/","title":{"rendered":"2018 &#8211; TRPM8 Activation via 3-Iodothyronamine Blunts VEGF-Induced Transactivation of TRPV1 in Human Uveal Melanoma Cells"},"content":{"rendered":"<p>In human uveal melanoma (UM), tumor enlargement is associated with increases in aqueous humor vascular endothelial growth factor-A (VEGF-A) content that induce neovascularization. 3-Iodothyronamine (3-T1AM), an endogenous thyroid hormone metabolite, activates TRP melastatin 8 (TRPM8), which blunts TRP vanilloid 1 (TRPV1) activation by capsaicin (CAP) in human corneal, conjunctival epithelial cells, and stromal cells. We compare here the effects of TRPM8 activation on VEGF-induced transactivation of TRPV1 in an UM cell line (92.1) with those in normal primary porcine melanocytes (PM) since TRPM8 is upregulated in melanoma. Fluorescence Ca<sup>2+<\/sup>-imaging and planar patch-clamping characterized functional channel activities. CAP (20 \u03bcM) induced Ca<sup>2+<\/sup> transients and increased whole-cell currents in both the UM cell line and PM whereas TRPM8 agonists, 100 \u03bcM menthol and 20 \u03bcM icilin, blunted such responses in the UM cells. VEGF (10 ng\/ml) elicited Ca<sup>2+<\/sup> transients and augmented whole-cell currents, which were blocked by capsazepine (CPZ; 20 \u03bcM) but not by a highly selective TRPM8 blocker, AMTB (20 \u03bcM). The VEGF-induced current increases were not augmented by CAP. Both 3-T1AM (1 \u03bcM) and menthol (100 \u03bcM) increased the whole-cell currents, whereas 20 \u03bcM AMTB blocked them. 3-T1AM exposure suppressed both VEGF-induced Ca<sup>2+<\/sup> transients and increases in underlying whole-cell currents. Taken together, functional TRPM8 upregulation in UM 92.1 cells suggests that TRPM8 is a potential drug target for suppressing VEGF induced increases in neovascularization and UM tumor growth since TRPM8 activation blocked VEGF transactivation of TRPV1.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[45],"resource_type":[75],"application_areas":[50,76],"therapeutic_areas":[57],"target_categories":[337,338],"target_families":[339],"targets":[101,122],"resource_keyword":[],"class_list":["post-6280","resource_library","type-resource_library","status-publish","hentry","products_tags-port-a-patch","resource_type-publication","application_areas-ion-channels","application_areas-drug-discovery","therapeutic_areas-cancer","target_categories-ligand-gated-ion-channels","target_categories-other-ion-channels","target_families-trp-channels","targets-trpv1","targets-trpm8"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library\/6280","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library"}],"about":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/types\/resource_library"}],"wp:attachment":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/media?parent=6280"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/products_tags?post=6280"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_type?post=6280"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/application_areas?post=6280"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/therapeutic_areas?post=6280"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_categories?post=6280"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_families?post=6280"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/targets?post=6280"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_keyword?post=6280"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}