ArticleMolecular metabolism2020
Metabolic insights from a GHSR-A203E mutant mouse model.
Article in Molecular metabolism, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 45 citations in OpenAlex.
- Recent developments in GPCR signalling in appetite regulation.Bioscience reports · 2026Review
- Review
- MRAP2 potentiates GPCR signaling by conserved mechanisms that are disrupted by obesity-associated genetic variants.bioRxiv : the preprint server for biology · 2025Article
- Temporal control of eating and body weight by GHSR-expressing suprachiasmatic nucleus neurons.Cell reports · 2025Article
- Loss-of-Function GHSR Variants Are Associated With Short Stature and Low IGF-I.The Journal of clinical endocrinology and metabolism · 2025Article
- Increased GHS-R1a expression in the hippocampus impairs memory encoding and contributes to AD-associated memory deficits.Communications biology · 2024Article
- Ligand-Free Signaling of G-Protein-Coupled Receptors: Physiology, Pharmacology, and Genetics.Molecules (Basel, Switzerland) · 2023Review
- Chlorpromazine, an Inverse Agonist of D1R-Like, Differentially Targets Voltage-Gated Calcium Channel (CaMolecular neurobiology · 2023Article
- Ghrelin receptor signaling in health and disease: a biased view.Trends in endocrinology and metabolism: TEM · 2023Review
- Sustained inhibition of NPY/AgRP neuronal activity by FGF1.JCI insight · 2022Article
- Binding Domain Characterization of Growth Hormone Secretagogue Receptor.Journal of translational internal medicine · 2022Article
- Targeting the Gut in Obesity: Signals from the Inner Surface.Metabolites · 2022Review
- The emerging role of heterodimerisation and interacting proteins in ghrelin receptor function.The Journal of endocrinology · 2021Review
- Selectively increasing GHS-R1a expression in dCA1 excitatory/inhibitory neurons have opposite effects on memory encoding.Molecular brain · 2021Article
- Contribution of Ghrelin to the Pathogenesis of Growth Hormone Deficiency.International journal of molecular sciences · 2021Review
- "A LEAP 2 conclusions? Targeting the ghrelin system to treat obesity and diabetes".Molecular metabolism · 2021Review
- LEAP2 Impairs the Capability of the Growth Hormone Secretagogue Receptor to Regulate the Dopamine 2 Receptor Signaling.Frontiers in pharmacology · 2021Article
- Ninjin'yoeito Targets Distinct CaFrontiers in nutrition · 2020Article
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Authors and funding
18 authors at 3 institutions in 3 countries.
Funding
Abstract
objectiveBinding of ghrelin to its receptor, growth hormone secretagogue receptor (GHSR), stimulates GH release, induces eating, and increases blood glucose. These processes may also be influenced by constitutive (ghrelin-independent) GHSR activity, as suggested by findings in short people with naturally occurring GHSR-A204E mutations and reduced food intake and blood glucose in rodents administered GHSR inverse agonists, both of which impair constitutive GHSR activity. In this study, we aimed to more fully determine the physiologic relevance of constitutive GHSR activity.
methodsWe generated mice with a GHSR mutation that replaces alanine at position 203 with glutamate (GHSR-A203E), which corresponds to the previously described human GHSR-A204E mutation, and used them to conduct ex vivo neuronal electrophysiology and in vivo metabolic assessments. We also measured signaling within COS-7 and HEK293T cells transfected with wild-type GHSR (GHSR-WT) or GHSR-A203E constructs.
resultsIn COS-7 cells, GHSR-A203E resulted in lower baseline IP
conclusionsOur data suggest that the A203E mutation ablates constitutive GHSR activity and that constitutive GHSR activity contributes to the native depolarizing conductance of GHSR-expressing arcuate NPY neurons. Although the A203E mutation does not block ghrelin-evoked signaling as assessed using in vitro and ex vivo models, GHSR-A203E mice lack the usual acute food intake response to administered ghrelin in vivo. The GHSR-A203E mutation also blunts GH release, and in aged mice leads to reduced body length and femur length, which are consistent with the short stature of human carriers of the GHSR-A204E mutation.
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Registered trials
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