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Growth Hormone Secretagogue Receptor Dimers: A New Pharmacological Target(1,2,3).

Wellman M, Abizaid A - eNeuro (2015)

Bottom Line: 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 disease, schizophrenia, addiction, obesity, diabetes, and more, can be devised.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neuroscience, Carleton University , Ottawa, Ontario, Canada , K1S 5B6.

ABSTRACT
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 disease, 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.

No MeSH data available.


Related in: MedlinePlus

Selected areas of interest involving possible GHSR1a dimers along with postulated roles/treatments. Brain figure adapted from the Allen Mouse Brain Atlas (Lein et al., 2007).
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Figure 6: Selected areas of interest involving possible GHSR1a dimers along with postulated roles/treatments. Brain figure adapted from the Allen Mouse Brain Atlas (Lein et al., 2007).

Mentions: As summarized in Figure 6, the dimer partners discussed in this review provide hints as to possible treatment targets for various disorders and conditions. In some cases, these treatments could involve the use of multiple drugs to provide a synergistic effect, amplifying the effect seen when only one drug is administered. In others, supplementing a treatment with an amplifying agent may have beneficial off-target effects beyond synergy. In such cases, not only do these treatments amplify neurotransmitter receptor signaling, but they may have other possible effects such as reduction in depression, neuroprotection, and stimulation of appetite—all effects that may relate to the effects on GHSR alone and not the dimer. The identification of GHSR heterodimers certainly opens the door for potential new treatments and treatment adjuvants that could improve a number of chronic psychiatric and metabolic conditions.


Growth Hormone Secretagogue Receptor Dimers: A New Pharmacological Target(1,2,3).

Wellman M, Abizaid A - eNeuro (2015)

Selected areas of interest involving possible GHSR1a dimers along with postulated roles/treatments. Brain figure adapted from the Allen Mouse Brain Atlas (Lein et al., 2007).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4596092&req=5

Figure 6: Selected areas of interest involving possible GHSR1a dimers along with postulated roles/treatments. Brain figure adapted from the Allen Mouse Brain Atlas (Lein et al., 2007).
Mentions: As summarized in Figure 6, the dimer partners discussed in this review provide hints as to possible treatment targets for various disorders and conditions. In some cases, these treatments could involve the use of multiple drugs to provide a synergistic effect, amplifying the effect seen when only one drug is administered. In others, supplementing a treatment with an amplifying agent may have beneficial off-target effects beyond synergy. In such cases, not only do these treatments amplify neurotransmitter receptor signaling, but they may have other possible effects such as reduction in depression, neuroprotection, and stimulation of appetite—all effects that may relate to the effects on GHSR alone and not the dimer. The identification of GHSR heterodimers certainly opens the door for potential new treatments and treatment adjuvants that could improve a number of chronic psychiatric and metabolic conditions.

Bottom Line: 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 disease, schizophrenia, addiction, obesity, diabetes, and more, can be devised.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neuroscience, Carleton University , Ottawa, Ontario, Canada , K1S 5B6.

ABSTRACT
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 disease, 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.

No MeSH data available.


Related in: MedlinePlus