dc.contributor.author
Bräunig, Julia
dc.contributor.author
Dinter, Juliane
dc.contributor.author
Höfig, Carolin S.
dc.contributor.author
Paisdzior, Sarah
dc.contributor.author
Szczepek, Michal
dc.contributor.author
Scheerer, Patrick
dc.contributor.author
Rosowski, Mark
dc.contributor.author
Mittag, Jens
dc.contributor.author
Kleinau, Gunnar
dc.contributor.author
Biebermann, Heike
dc.date.accessioned
2019-04-18T09:54:43Z
dc.date.available
2019-04-18T09:54:43Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/24457
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-2228
dc.description.abstract
Trace amine-associated receptors (TAARs) belong to the class A G-protein-coupled receptors (GPCR) and are evolutionary related to aminergic receptors. TAARs have been identified to mediate effects of trace amines. TAAR1 signaling is mainly mediated via activation of the G(s)/adenylyl cyclase pathway. In addition to classical trace amines, TAAR1 can also be activated by the thyroid hormone derivative 3-iodothyronamine (3-T1AM). Pharmacological doses of 3-T1AM induced metabolic and anapyrexic effects, which might be centrally mediated in the hypothalamus in rodents. However, the observed anapyrexic effect of 3-T1AM persists in Taar1 knock-out mice which raises the question whether further GPCRs are potential targets for 3-T1AM and mediate the observed physiological effect. Anapyrexia has been observed to be related to action on aminergic receptors such as the serotonin receptor 1b (5-HT1b). This receptor primarily activates the G(i/o) mediated pathway and PLC signaling through the G(beta gamma) of G(i/o). Since the expression profiles of TAAR1 and 5-HT1b overlap, we questioned whether 3-T1AM may activate 5-HT1b. Finally, we also evaluated heteromerization between these two GPCRs and tested signaling under co-expressed conditions. In this study, we showed, that 3-T1AM can induce G(i/o) signaling through 5-HT1b in a concentration of 10 mu M. Strikingly, at 5-HT1b the ligand 3-T1AM only activates the G(i/o) mediated reduction of cAMP accumulation, but not PLC activation. Co-stimulation of 5-HT1b by both ligands did not lead to additive or synergistic signaling effects. In addition, we confirmed the capacity for heteromerization between TAAR1 and 5-HT1b. Under co-expression of TAAR1 and HTR1b, 3-T1AM action is only mediated via TAAR1 and activation of 5-HT1b is abrogated. In conclusion, we found evidence for 5-HT1b as a new receptor target for 3-T1AM, albeit with a different signaling effect than the endogenous ligand. Altogether, this indicates a complex interrelation of signaling effects between the investigated GPCRs and respective ligands.
en
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
trace amine-associated receptor 1 (TAAR1)
en
dc.subject
serotonin receptor lb (5-HT1b)
en
dc.subject
signal transduction
en
dc.subject
biased signaling
en
dc.subject
trace amines
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
dc.title
The Trace Amine-Associated Receptor 1 Agonist 3-lodothyronamine Induces Biased Signaling at the Serotonin 1 b Receptor
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.articlenumber
222
dcterms.bibliographicCitation.doi
10.3389/fphar.2018.00222
dcterms.bibliographicCitation.journaltitle
Frontiers in Pharmacology
dcterms.bibliographicCitation.originalpublishername
Frontiers Media S.A.
dcterms.bibliographicCitation.volume
9
refubium.affiliation
Charité - Universitätsmedizin Berlin
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.bibliographicCitation.pmid
29593543
dcterms.isPartOf.issn
1663-9812