Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1932121 | Biochemical and Biophysical Research Communications | 2010 | 6 Pages |
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 Gi/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.