ArticleThe Journal of biological chemistry2013
Promiscuous dimerization of the growth hormone secretagogue receptor (GHS-R1a) attenuates ghrelin-mediated signaling.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed.
- A biopsychosocial perspective on obesity and eating disorders: A narrative overview and exploratory study of ghrelin, LEAP2, trait impulsivity, and eating psychopathology.Reviews in endocrine & metabolic disorders · 2026Review
- Activation of GHSRs Facilitates the Excitability of Dentate Gyrus Granule Cells and Short-Term Spatial Memory via Multiple Ionic and Signaling Mechanisms.Advanced biology · 2026Article
- GHSR antagonist LEAP2 concentrations negatively correlate with alcohol craving and are modulated by alcohol exposure: Evidence from human and rat studies.Drug and alcohol dependence · 2026Article
- A Dimer for Dinner: The Impact of GHS-R1a Heterodimerization on Feeding Circuits.Biomolecules · 2026Review
- Characterizing ghrelin's role in dysregulating GLP-1-mediated function and promoting the development of alcohol-associated liver disease.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2026Article
- Ghrelin Increases Glutamate Release at the Perforant Path-Dentate Gyrus Granule Cell Synapses by Cross-Activating Dopamine DJournal of cellular physiology · 2025Article
- An Emerging Role for Gut-Brain Signaling Involving Ghrelin in Chronic Stress.Advances in experimental medicine and biology · 2025Review
- Increased GHS-R1a expression in the hippocampus impairs memory encoding and contributes to AD-associated memory deficits.Communications biology · 2024Article
- Quinpirole ameliorates nigral dopaminergic neuron damage in Parkinson's disease mouse model through activating GHS-R1a/DActa pharmacologica Sinica · 2023Article
- Establishment of a Cell Line Stably Expressing the Growth Hormone Secretagogue Receptor to Identify Crocin as a Ghrelin Agonist.Biomolecules · 2022Article
- Ghrelin infusion into the basolateral amygdala suppresses CTA memory formation in rats via the PI3K/Akt/mTOR and PLC/PKC signaling pathways.Acta pharmacologica Sinica · 2022Article
- Ghrelin rapidly elevates protein synthesis in vitro by employing the rpS6K-eEF2K-eEF2 signalling axis.Cellular and molecular life sciences : CMLS · 2022Article
- Review
- The Role of Ghrelin/GHS-R1A Signaling in Nonalcohol Drug Addictions.International journal of molecular sciences · 2022Review
- The oxytocin receptor represents a key hub in the GPCR heteroreceptor network: potential relevance for brain and behavior.Frontiers in molecular neuroscience · 2022Review
- The emerging role of heterodimerisation and interacting proteins in ghrelin receptor function.The Journal of endocrinology · 2021Review
- Olanzapine Administration Reduces Chemotherapy-Induced Nausea Behavior in Rats.Biological research for nursing · 2021Article
- Relationship between Orexigenic Peptide Ghrelin Signal, Gender Difference and Disease.International journal of molecular sciences · 2021Review
- "A LEAP 2 conclusions? Targeting the ghrelin system to treat obesity and diabetes".Molecular metabolism · 2021Review
- The Benefits of Olanzapine in Palliating Symptoms.Current treatment options in oncology · 2020Review
6 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
G protein-coupled receptors (GPCRs), such as the ghrelin receptor (GHS-R1a), the melanocortin 3 receptor (MC(3)), and the serotonin 2C receptor (5-HT(2C)), are well known for their key role in the homeostatic control of food intake and energy balance. Ghrelin is the only known gut peptide exerting an orexigenic effect and has thus received much attention as an anti-obesity drug target. In addition, recent data have revealed a critical role for ghrelin in dopaminergic mesolimbic circuits involved in food reward signaling. This study investigates the downstream signaling consequences and ligand-mediated co-internalization following heterodimerization of the GHS-R1a receptor with the dopamine 1 receptor, as well as that of the GHS-R1a-MC(3) heterodimer. In addition, a novel heterodimer between the GHS-R1a receptor and the 5-HT(2C) receptor was identified. Interestingly, dimerization of the GHS-R1a receptor with the unedited 5-HT(2C)-INI receptor, but not with the partially edited 5-HT(2C)-VSV isoform, significantly reduced GHS-R1a agonist-mediated calcium influx, which was completely restored following pharmacological blockade of the 5-HT(2C) receptor. These results combined suggest a potential novel mechanism for fine-tuning GHS-R1a receptor-mediated activity via promiscuous dimerization of the GHS-R1a receptor with other G protein-coupled receptors involved in appetite regulation and food reward. These findings may uncover novel mechanisms of significant relevance for the future pharmacological targeting of the GHS-R1a receptor in the homeostatic regulation of energy balance and in hedonic appetite signaling, both of which play a significant role in the development of obesity.
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