ArticleThe Journal of biological chemistry2012
High constitutive activity is an intrinsic feature of ghrelin receptor protein: a study with a functional monomeric GHS-R1a receptor reconstituted in lipid discs.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 152 citations in OpenAlex.
- Trial
- Myeloid GHSR Deficiency Protects Against Endotoxemia via Macrophage Mitochondrial Reprogramming.Biomedicines · 2026Article
- Meta-inflammation through the lens of macrophage programming and nutrient-sensing ghrelin signaling.Immunometabolism (Cobham, Surrey) · 2026Review
- A Dimer for Dinner: The Impact of GHS-R1a Heterodimerization on Feeding Circuits.Biomolecules · 2026Review
- Membrane cholesterol modulates engagement of β-arrestin with the ghrelin receptor.Communications biology · 2026Article
- Studies of Foxo1 over the Past 25 Years: Mechanisms of Insulin Resistance and Glucose Dysregulation.Cells · 2026Review
- Beyond Hunger: The Structure, Signaling, and Systemic Roles of Ghrelin.International journal of molecular sciences · 2025Review
- Synthesis and Pharmacological Characterization of a Novel Cannabinoid Receptor 1 Antagonist.ACS omega · 2025Article
- Lipids modulate the dynamics of GPCR:β-arrestin interaction.Nature communications · 2025Article
- Insights on discovery, efficacy, safety and clinical applications of ghrelin receptor agonist capromorelin in veterinary medicine.Veterinary research communications · 2024Review
- The adhesion GPCR GPR116/ADGRF5 has a dual function in pancreatic islets regulating somatostatin release and islet development.Communications biology · 2024Article
- Pharmacological GHSR (ghrelin receptor) blockade reduces alcohol binge-like drinking in male and female mice.Neuropharmacology · 2023Article
- Quinpirole ameliorates nigral dopaminergic neuron damage in Parkinson's disease mouse model through activating GHS-R1a/DActa pharmacologica Sinica · 2023Article
- Article
- Discovery of Ghrelin(1-8) Analogues with Improved Stability and Functional Activity for PET Imaging.ACS pharmacology & translational science · 2023Article
- Ghrelin receptor signaling in health and disease: a biased view.Trends in endocrinology and metabolism: TEM · 2023Review
- Glycine Effect on the Expression Profile of Orphan Receptors GPR21, GPR26, GPR39, GPR82 and GPR6 in a Model of Inflammation in 3T3-L1 Cells.Life (Basel, Switzerland) · 2022Article
- Transcriptional adaptation of olfactory sensory neurons to GPCR identity and activity.Nature communications · 2022Article
- Functional divergence of the pigmentation gene melanocortin-1 receptor (MC1R) in six endemic Macaca species on Sulawesi Island.Scientific reports · 2022Article
- "Sibling" battle or harmony: crosstalk between nesfatin-1 and ghrelin.Cellular and molecular life sciences : CMLS · 2022Review
12 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite its central role in signaling and the potential therapeutic applications of inverse agonists, the molecular mechanisms underlying G protein-coupled receptor (GPCR) constitutive activity remain largely to be explored. In this context, ghrelin receptor GHS-R1a is a peculiar receptor in the sense that it displays a strikingly high, physiologically relevant, constitutive activity. To identify the molecular mechanisms responsible for this high constitutive activity, we have reconstituted a purified GHS-R1a monomer in a lipid disc. Using this reconstituted system, we show that the isolated ghrelin receptor per se activates G(q) in the absence of agonist, as assessed through guanosine 5'-O-(thiotriphosphate) binding experiments. The measured constitutive activity is similar in its extent to that observed in heterologous systems and in vivo. This is the first direct evidence for the high constitutive activity of the ghrelin receptor being an intrinsic property of the protein rather than the result of influence of its cellular environment. Moreover, we show that the isolated receptor in lipid discs recruits arrestin-2 in an agonist-dependent manner, whereas it interacts with μ-AP2 in the absence of ligand or in the presence of ghrelin. Of importance, these differences are linked to ligand-specific GHS-R1a conformations, as assessed by intrinsic fluorescence measurements. The distinct ligand requirements for the interaction of purified GHS-R1a with arrestin and AP2 provide a new rationale to the differences in basal and agonist-induced internalization observed in cells.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.