TY - JOUR T1 - Growth Hormone Secretagogue Receptor Dimers: A New Pharmacological Target JF - eneuro JO - eneuro DO - 10.1523/ENEURO.0053-14.2015 SP - ENEURO.0053-14.2015 AU - Martin Wellman AU - Alfonso Abizaid Y1 - 2015/04/14 UR - http://www.eneuro.org/content/early/2015/04/14/ENEURO.0053-14.2015.abstract N2 - The growth hormone secretagogue receptor (GHSR1a), the target of the ghrelin peptide, is widely distributed throughout the brain, and, while studies have often reported very low or absent levels of central ghrelin, it is now known that GHSR1a, even in the absence of a natural ligand, has physiological roles. Not only do these roles originate from the receptor’s constitutive activity, but recent data indicate that GHSR1a dimerizes with a wide array of other receptors. These include the dopamine 1 receptor (D1R), the dopamine 2 receptor (D2R), the melanocortin-3 receptor (MC3R), the serotonin 2C receptor (5-HT2C), and possibly the cannabinoid type 1 receptor (CB1). Within these dimers, signaling of the protomers involved are modified through facilitation, inhibition, and even modification of signaling pathways resulting in physiological consequences not seen in the absence of these dimers. While in some cases the ghrelin peptide is not required for these modifications to occur, in others, the presence is necessary for these changes to take effect. These heterodimers demonstrate the broad array of roles and complexity of the ghrelin system. By better understanding how these dimers work it is hoped that improved treatments for a variety of disorders, including Parkinson’s, schizophrenia, addiction, obesity, diabetes, and more, can be devised. In this review, we examine the current state of knowledge surrounding GHSR heterodimers, and how we can apply this knowledge to various pharmacological treatments. Significance Statement: The growth hormone secretagogue receptor is a key component of the ghrelin system important in many processes including feeding behavior, stress, and reward. Recent data have revealed a variety of receptors that show the ability to dimerize with the ghrelin receptor, resulting in signal modulation, alterations in signaling cascades, and changes in trafficking and internalization of both protomers of the dimer complex. Here, we summarize the state of knowledge surrounding ghrelin receptor dimerization, along with potential treatments that arise from this knowledge for a variety of disorders, demonstrating the importance of understanding these dimer complexes. ER -