ArticleMolecular endocrinology (Baltimore, Md.)2013
β-arrestin-selective G protein-coupled receptor agonists engender unique biological efficacy in vivo.
Article in Molecular endocrinology (Baltimore, Md.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed, 59 citations in OpenAlex.
- Agonism and Biased Signaling.Handbook of experimental pharmacology · 2026Review
- GPCR systems coordinate cellular resilience against aging-associated stress.Frontiers in molecular biosciences · 2026Review
- Intersection of the Orphan G Protein-Coupled Receptor, GPR19, with the Aging Process.International journal of molecular sciences · 2022Review
- The Relaxin-3 Receptor, RXFP3, Is a Modulator of Aging-Related Disease.International journal of molecular sciences · 2022Review
- GPCRs Are Optimal Regulators of Complex Biological Systems and Orchestrate the Interface between Health and Disease.International journal of molecular sciences · 2021Review
- Key phosphorylation sites in GPCRs orchestrate the contribution of β-Arrestin 1 in ERK1/2 activation.EMBO reports · 2020Article
- The RXFP3 receptor is functionally associated with cellular responses to oxidative stress and DNA damage.Aging · 2019Article
- G Protein-Coupled Receptor Systems and Their Role in Cellular Senescence.Computational and structural biotechnology journal · 2019Review
- Structure-inspired design of β-arrestin-biased ligands for aminergic GPCRs.Nature chemical biology · 2018Article
- Translating in vitro ligand bias into in vivo efficacy.Cellular signalling · 2018Review
- β-Arrestin Based Receptor Signaling Paradigms: Potential Therapeutic Targets for Complex Age-Related Disorders.Frontiers in pharmacology · 2018Review
- G Protein-Coupled Receptor Signaling Through β-Arrestin-Dependent Mechanisms.Journal of cardiovascular pharmacology · 2017Review
- The Diverse Roles of Arrestin Scaffolds in G Protein-Coupled Receptor Signaling.Pharmacological reviews · 2017Review
- Functional selectivity at G-protein coupled receptors: Advancing cannabinoid receptors as drug targets.Biochemical pharmacology · 2017Review
- G Protein-Coupled Receptor Endocytosis Confers Uniformity in Responses to Chemically Distinct Ligands.Molecular pharmacology · 2017Article
- The Multiple Waves of Cannabinoid 1 Receptor Signaling.Molecular pharmacology · 2016Review
- Angiotensin II receptors and peritoneal dialysis-induced peritoneal fibrosis.The international journal of biochemistry & cell biology · 2016Review
- Informatic deconvolution of biased GPCR signaling mechanisms from in vivo pharmacological experimentation.Methods (San Diego, Calif.) · 2016Article
- Exploring G protein-coupled receptor signaling networks using SILAC-based phosphoproteomics.Methods (San Diego, Calif.) · 2016Article
- Fulfilling the Promise of "Biased" G Protein-Coupled Receptor Agonism.Molecular pharmacology · 2015Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Biased G protein-coupled receptor agonists are orthosteric ligands that possess pathway-selective efficacy, activating or inhibiting only a subset of the signaling repertoire of their cognate receptors. In vitro, D-Trp(12),Tyr(34)-bPTH(7-34) [bPTH(7-34)], a biased agonist for the type 1 PTH receptor, antagonizes receptor-G protein coupling but activates arrestin-dependent signaling. In vivo, both bPTH(7-34) and the conventional agonist hPTH(1-34) stimulate anabolic bone formation. To understand how two PTH receptor ligands with markedly different in vitro efficacy could elicit similar in vivo responses, we analyzed transcriptional profiles from calvarial bone of mice treated for 8 wk with vehicle, bPTH(7-34) or hPTH(1-34). Treatment of wild-type mice with bPTH(7-34) primarily affected pathways that promote expansion of the osteoblast pool, notably cell cycle regulation, cell survival, and migration. These responses were absent in β-arrestin2-null mice, identifying them as downstream targets of β-arrestin2-mediated signaling. In contrast, hPTH(1-34) primarily affected pathways classically associated with enhanced bone formation, including collagen synthesis and matrix mineralization. hPTH(1-34) actions were less dependent on β-arrestin2, as might be expected of a ligand capable of G protein activation. In vitro, bPTH(7-34) slowed the rate of preosteoblast proliferation, enhanced osteoblast survival when exposed to an apoptotic stimulus, and stimulated cell migration in wild-type, but not β-arrestin2-null, calvarial osteoblasts. These results suggest that bPTH(7-34) and hPTH(1-34) affect bone mass in vivo through predominantly separate genomic mechanisms created by largely distinct receptor-signaling networks and demonstrate that functional selectivity can be exploited to change the quality of G protein-coupled receptor efficacy.
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What OpenQuestion holds
Registered trials
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.