ArticleThe Journal of biological chemistry2012
Functional selective oxytocin-derived agonists discriminate between individual G protein family subtypes.
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 82 papers.
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Who cites it
82 citing papers in PubMed, 183 citations in OpenAlex.
- Oxytocin increases eye gaze in schizophrenia.Schizophrenia research · 2019Trial
- Oxytocin Variants Induce Cellular Signaling and Neurite Outgrowth in Human-Derived Neuron-like SH-SY5Y Cell Line.NeuroSci · 2026Article
- Sex-specific regulation of social play in juvenile rats by oxytocin neurons in the hypothalamus and oxytocin signaling in the nucleus accumbens.Hormones and behavior · 2026Article
- Article
- Novel GαGTP Sensors Reveal Endogenous and Subcellular G Protein Signaling Dynamics.bioRxiv : the preprint server for biology · 2026Article
- Circuit logic of oxytocin and vasopressin complementary actions.Frontiers in neuroscience · 2026Review
- Context-dependent oxytocin receptor signaling: from molecular architecture to transcript-level receptor engineering.Frontiers in neuroscience · 2026Review
- Stress induces oxytocin-Gαi-dependent remodeling of astrocytes to shape neuronal response in the amygdala.Nature communications · 2025Article
- Interaction Between Oxytocin and Dopamine Signaling: Focus on the Striatum.International journal of molecular sciences · 2025Review
- Oxytocin in the Amygdala Sustains Prosocial Behavior via State-Dependent Amygdala-Prefrontal Modulation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Dual Oxytocin Signals in Striatal Astrocytes.Biomolecules · 2025Article
- PVN-NAc Shell-VP Circuit OT and OTR Neurons Regulate Pair Bonding via D2R and D1R.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Navigating Central Oxytocin Transport: Known Realms and Uncharted Territories.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2025Review
- The Relationship Between Oxytocin and Alcohol Dependence.Current topics in behavioral neurosciences · 2025Review
- Predicting oxytocin binding dynamics in receptor genetic variants through computational modeling.npj women's health · 2025Article
- Article
- Activation of Multiple G Protein Pathways to Characterize the Five Dopamine Receptor Subtypes Using Bioluminescence Technology.ACS pharmacology & translational science · 2024Article
- Specific pharmacological and GNature communications · 2024Article
- Targeting the Oxytocin Receptor for Breast Cancer Management: A Niche for Peptide Tracers.Journal of medicinal chemistry · 2024Review
- Role of the adenylate cyclase/cyclic AMP pathway in oxytocin-induced lacrimal gland myoepithelial cells contraction.Experimental eye research · 2023Article
22 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 5 institutions in 4 countries.
Funding
Abstract
We used a bioluminescence resonance energy transfer biosensor to screen for functional selective ligands of the human oxytocin (OT) receptor. We demonstrated that OT promoted the direct engagement and activation of G(q) and all the G(i/o) subtypes at the OT receptor. Other peptidic analogues, chosen because of specific substitutions in key OT structural/functional residues, all showed biased activation of G protein subtypes. No ligand, except OT, activated G(oA) or G(oB), and, with only one exception, all of the peptides that activated G(q) also activated G(i2) and G(i3) but not G(i1), G(oA), or G(oB), indicating a strong bias toward these subunits. Two peptides (DNalOVT and atosiban) activated only G(i1) or G(i3), failed to recruit β-arrestins, and did not induce receptor internalization, providing the first clear examples of ligands differentiating individual G(i/o) family members. Both analogs inhibited cell proliferation, showing that a single G(i) subtype-mediated pathway is sufficient to prompt this physiological response. These analogs represent unique tools for examining the contribution of G(i/o) members in complex biological responses and open the way to the development of drugs with peculiar selectivity profiles. This is of particular relevance because OT has been shown to improve symptoms in neurodevelopmental and psychiatric disorders characterized by abnormal social behaviors, such as autism. Functional selective ligands, activating a specific G protein signaling pathway, may possess a higher efficacy and specificity on OT-based therapeutics.
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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.