Dinter, J.* ; Mühlhaus, J.* ; Wienchol, C.L.* ; Yi, C.-X. ; Nürnberg, D.* ; Morin, S. ; Grüters, A.* ; Köhrle, J.* ; Schöneberg, T.* ; Tschöp, M.H.* ; Krude, H.* ; Kleinau, G.* ; Biebermann, H.*
     
 
    
        
Inverse agonistic action of 3-iodothyronamine at the human trace amine-associated receptor 5.
    
    
        
    
    
        
        PLoS ONE 10:e0117774 (2015)
    
    
    
		
		
			
				OBJECTIVE: Application of 3-iodothyronamine (3-T1AM) results in decreased body temperature and body weight in rodents. The trace amine-associated receptor (TAAR) 1, a family A G protein-coupled receptor, is a target of 3-T1AM. However, 3-T1AM effects still persist in mTaar1 knockout mice, which suggest so far unknown further receptor targets that are of physiological relevance. TAAR5 is a highly conserved TAAR subtype among mammals and we here tested TAAR5 as a potential 3-T1AM target. First, we investigated mouse Taar5 (mTaar5) expression in several brain regions of the mouse in comparison to mTaar1. Secondly, to unravel the full spectrum of signaling capacities, we examined the distinct Gs-, Gi/o-, G12/13-, Gq/11- and MAP kinase-mediated signaling pathways of mouse and human TAAR5 under ligand-independent conditions and after application of 3-T1AM. We found overlapping localization of mTaar1 and mTaar5 in the amygdala and ventromedial hypothalamus of the mouse brain. Second, the murine and human TAAR5 (hTAAR5) display significant basal activity in the Gq/11 pathway but show differences in the basal activity in Gs and MAP kinase signaling. In contrast to mTaar5, 3-T1AM application at hTAAR5 resulted in significant reduction in basal IP3 formation and MAP kinase signaling. In conclusion, our data suggest that the human TAAR5 is a target for 3-T1AM, exhibiting inhibitory effects on IP3 formation and MAP kinase signaling pathways, but does not mediate Gs signaling effects as observed for TAAR1. This study also indicates differences between TAAR5 orthologs with respect to their signaling profile. In consequence, 3-T1AM-mediated effects may differ between rodents and humans.
			
			
				
			
		 
		
			
				
					
					Impact Factor
					Scopus SNIP
					Web of Science
Times Cited
					Scopus
Cited By
					
					Altmetric
					
				 
				
			 
		 
		
     
    
        Publikationstyp
        Artikel: Journalartikel
    
 
    
        Dokumenttyp
        Wissenschaftlicher Artikel
    
 
    
        Typ der Hochschulschrift
        
    
 
    
        Herausgeber
        
    
    
        Schlagwörter
        Protein-coupled Receptors; Hormone Derivative 3-iodothyronamine; Adipose-tissue Thermogenesis; Thyroid-hormone; Olfactory Subsystem; Hypothalamic Ampk; Molecular-basis; Metabolism; Expression; Cells
    
 
    
        Keywords plus
        
    
 
    
    
        Sprache
        englisch
    
 
    
        Veröffentlichungsjahr
        2015
    
 
    
        Prepublished im Jahr 
        
    
 
    
        HGF-Berichtsjahr
        2015
    
 
    
    
        ISSN (print) / ISBN
        1932-6203
    
 
    
        e-ISSN
        
    
 
    
        ISBN
        
    
 
    
        Bandtitel
        
    
 
    
        Konferenztitel
        
    
 
	
        Konferzenzdatum
        
    
     
	
        Konferenzort
        
    
 
	
        Konferenzband
        
    
 
     
		
    
        Quellenangaben
        
	    Band: 10,  
	    Heft: 2,  
	    Seiten: ,  
	    Artikelnummer: e0117774 
	    Supplement: ,  
	
    
 
  
        
            Reihe
            
        
 
        
            Verlag
            Public Library of Science (PLoS)
        
 
        
            Verlagsort
            Lawrence, Kan.
        
 
	
        
            Tag d. mündl. Prüfung
            0000-00-00
        
 
        
            Betreuer
            
        
 
        
            Gutachter
            
        
 
        
            Prüfer
            
        
 
        
            Topic
            
        
 
	
        
            Hochschule
            
        
 
        
            Hochschulort
            
        
 
        
            Fakultät
            
        
 
    
        
            Veröffentlichungsdatum
            0000-00-00
        
 
         
        
            Anmeldedatum
            0000-00-00
        
 
        
            Anmelder/Inhaber
            
        
 
        
            weitere Inhaber
            
        
 
        
            Anmeldeland
            
        
 
        
            Priorität
            
        
 
    
        Begutachtungsstatus
        Peer reviewed
    
 
     
    
        POF Topic(s)
        30201 - Metabolic Health
90000 - German Center for Diabetes Research
    
 
    
        Forschungsfeld(er)
        Helmholtz Diabetes Center
    
 
    
        PSP-Element(e)
        G-502200-001
G-501900-221
    
 
    
        Förderungen
        
    
 
    
        Copyright
        
    
 	
    
    
    
    
    
        Erfassungsdatum
        2015-02-25