Galanin receptor-1 modulates 5-hydroxtryptamine-1A signaling via heterodimerization.
Biochem Biophys Res Commun
; 393(4): 767-72, 2010 Mar 19.
Article
en En
| MEDLINE
| ID: mdl-20171159
ABSTRACT
Previous biochemical, cardiovascular and behavioral work has given evidence for the existence of antagonistic galanin receptor-5-HT1A receptor interactions in the brain. In this study we investigated the existence of GalR1-5-HT1A receptor heteromers and their functional characteristics. In mammalian cells transfected with GFP2-tagged 5-HT1A receptor and YFP-tagged GalR1 receptor, a proximity-based fluorescence resonance energy transfer technique was used and it has been demonstrated that GalR1-5-HT1A receptors heteromerize. Furthermore, signaling by either the mitogen-activated protein kinase (MAPK) or adenylyl cyclase (AC) pathways by these heteromers indicates a trans-inhibition phenomenon through their interacting interface via allosteric mechanisms that block the development of an excessive activation of G(i/o) and an exaggerated inhibition of AC or stimulation of MAPK activity. The presence of these heteromers in the discrete brain regions is postulated based on the existence of GalR-5-HT1A receptor-receptor interactions previously described in the brain and gives rise to explore possible novel therapeutic strategies for treatment of depression by targeting the GalR1-5-HT1A heteromers.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Receptor de Galanina Tipo 1
/
Receptor de Serotonina 5-HT1A
Límite:
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2010
Tipo del documento:
Article
País de afiliación:
Suecia