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Basic Thyroidology / Original Paper

Free Access

The Multitarget Ligand 3-Iodothyronamine Modulates β-Adrenergic Receptor 2 Signaling

Dinter 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

Author affiliations

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

Corresponding Author

Heike Biebermann

Institut für Experimentelle Pädiatrische Endokrinologie

Charité-Universitätsmedizin Berlin, Augustenburger Platz 1

DE-13353 Berlin (Germany)

E-Mail heike.biebermann@charite.de

Stefan Mergler

Department of Ophthalmology, Charité-Universitätsmedizin Berlin

Augustenburger Platz 1

DE-13353 Berlin (Germany)

E-Mail Stefan.Mergler@charite.de

Related Articles for ""

Eur Thyroid J 2015;4(suppl 1):21-29

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Abstract

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- 10-10M) enhanced isoprenaline-induced ADRB2-mediated Gs signaling but not that of ADRB1-mediated signaling. MAPK signaling remained unaffected for both receptors. In IOBA-NHC cells, norepinephrine-induced Ca2+ influxes were blocked by the nonselective ADRB blocker timolol (10 µM), indicating that ADRBs are most likely linked with Ca2+ channels. Notably, timolol was also found to block 3-T1AM (10-5M)-induced Ca2+ influx. Conclusions: The presented data support that 3-T1AM directly modulates β-adrenergic receptor signaling. The relationship between 3-T1AM and β-adrenergic signaling also reveals a potential therapeutic value for suppressing Ca2+ channel-mediated inflammation processes, occurring in eye diseases such as conjunctivitis.

© 2015 European Thyroid Association Published by S. Karger AG, Basel


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Article / Publication Details

First-Page Preview
Abstract of Basic Thyroidology / Original Paper

Received: November 17, 2014
Accepted: March 19, 2015
Published online: May 29, 2015
Issue release date: September 2015

Number of Print Pages: 9
Number of Figures: 4
Number of Tables: 0

ISSN: 2235-0640 (Print)
eISSN: 2235-0802 (Online)

For additional information: https://www.karger.com/ETJ


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