Basic Thyroidology / Original Paper
The Multitarget Ligand 3-Iodothyronamine Modulates β-Adrenergic Receptor 2 SignalingDinter J.a · Khajavi N.b · Mühlhaus J.a · Wienchol C.L.a · Cöster M.d · Hermsdorf T.d · Stäubert C.d · Köhrle J.c · Schöneberg T.d · Kleinau G.a · Mergler S.b · Biebermann H.a
aInstitut für Experimentelle Pädiatrische Endokrinologie, bDepartment of Ophthalmology, and cInstitut für Experimentelle Endokrinologie, Charité-Universitätsmedizin Berlin, Berlin, and dInstitut für Biochemie, Molekulare Biochemie, Medizinische Fakultät, University of Leipzig, Leipzig, Germany
Institut für Experimentelle Pädiatrische Endokrinologie
Charité-Universitätsmedizin Berlin, Augustenburger Platz 1
DE-13353 Berlin (Germany)
Department of Ophthalmology, Charité-Universitätsmedizin Berlin
Augustenburger Platz 1
DE-13353 Berlin (Germany)
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Background: 3-Iodothyronamine (3-T1AM), a signaling molecule with structural similarities to thyroid hormones, induces numerous physiological responses including reversible body temperature decline. One target of 3-T1AM is the trace amine-associated receptor 1 (TAAR1), which is a member of the rhodopsin-like family of G protein-coupled receptors (GPCRs). Interestingly, the effects of 3-T1AM remain detectable in TAAR1 knockout mice, suggesting further targets for 3-T1AM such as adrenergic receptors. Therefore, we evaluated whether β-adrenergic receptor 1 (ADRB1) and 2 (ADRB2) signaling is affected by 3-T1AM in HEK293 cells and in human conjunctival epithelial cells (IOBA-NHC), where these receptors are highly expressed endogenously. Methods: A label-free EPIC system for prescreening the 3-T1AM-induced effects on ADRB1 and ADRB2 in transfected HEK293 cells was used. In addition, ADRB1 and ADRB2 activation was analyzed using a cyclic AMP assay and a MAPK reporter gene assay. Finally, fluorescence Ca2+ imaging was utilized to delineate 3-T1AM-induced Ca2+ signaling. Results: 3-T1AM (10-5- 10-10
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