ArticleThe Journal of biological chemistry2016
Human Neuropeptide S Receptor Is Activated via a Gαq Protein-biased Signaling Cascade by a Human Neuropeptide S Analog Lacking the C-terminal 10 Residues.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Neuropeptide S modulation of learning and memory: a systematic review.Behavioral and brain functions : BBF · 2026Pooled it
- Not Quite Folded: Challenges in Predicting the hNPS-hNPSR-Ile107 Complex With AlphaFold2 Multimer.ChemMedChem · 2026Article
- Neuropeptide S Protects Dopaminergic Neurons in a Paraquat-Induced Parkinson's Model Using SH-SY5Y Cells.Molecular neurobiology · 2026Article
- Neuropeptide S pathway in PTSD and neuropsychiatric disorders: A review.Biomolecules & biomedicine · 2025Review
- Selective G protein signaling driven by substance P-neurokinin receptor dynamics.Nature chemical biology · 2022Article
- Role of the Neuropeptide S System in Emotionality, Stress Responsiveness and Addiction-Like Behaviours in Rodents: Relevance to Stress-Related Disorders.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Neuropeptide S Receptor Stimulation Excites Principal Neurons in Murine Basolateral Amygdala through a Calcium-Dependent Decrease in Membrane Potassium Conductance.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Macrocyclic Gq Protein Inhibitors FR900359 and/or YM-254890-Fit for Translation?ACS pharmacology & translational science · 2021Article
- Advances in therapeutic peptides targeting G protein-coupled receptors.Nature reviews. Drug discovery · 2020Review
- Heterotrimeric GThe Journal of biological chemistry · 2020Review
- State-of-the-art: functional fluorescent probes for bioimaging and pharmacological research.Acta pharmacologica Sinica · 2019Review
- Rational design of a heterotrimeric G protein α subunit with artificial inhibitor sensitivity.The Journal of biological chemistry · 2019Article
- Pharmacological profile of the neuropeptide S receptor: Dynamic mass redistribution studies.Pharmacology research & perspectives · 2018Article
- Neuropeptide S Induces Acute Anxiolysis by Phospholipase C-Dependent Signaling within the Medial Amygdala.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Article
- Mitochondrial Dysfunctions Contribute to Hypertrophic Cardiomyopathy in Patient iPSC-Derived Cardiomyocytes with MT-RNR2 Mutation.Stem cell reports · 2018Article
- Neuropeptide S Activates Paraventricular Oxytocin Neurons to Induce Anxiolysis.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- Identification of the first biased NPS receptor agonist that retains anxiolytic and memory promoting effects with reduced levels of locomotor stimulation.Neuropharmacology · 2017Article
- Neuropeptide S (NPS) variants modify the signaling and risk effects of NPS Receptor 1 (NPSR1) variants in asthma.PloS one · 2017Article
- An experimental strategy to probe Gq contribution to signal transduction in living cells.The Journal of biological chemistryArticle
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Human neuropeptide S (NPS) and its cognate receptor regulate important biological functions in the brain and have emerged as a future therapeutic target for treatment of a variety of neurological and psychiatric diseases. The human NPS (hNPS) receptor has been shown to dually couple to Gαs- and Gαq-dependent signaling pathways. The human NPS analog hNPS-(1-10), lacking 10 residues from the C terminus, has been shown to stimulate Ca(2+)mobilization in a manner comparable with full-length hNPSin vitrobut seems to fail to induce biological activityin vivo Here, results derived from a number of cell-based functional assays, including intracellular cAMP-response element (CRE)-driven luciferase activity, Ca(2+)mobilization, and ERK1/2 phosphorylation, show that hNPS-(1-10) preferentially activates Gαq-dependent Ca(2+)mobilization while exhibiting less activity in triggering Gαs-dependent CRE-driven luciferase activity. We further demonstrate that both Gαq- and Gαs-coupled signaling pathways contribute to full-length hNPS-mediated activation of ERK1/2, whereas hNPS-(1-10)-promoted ERK1/2 activation is completely inhibited by the Gαqinhibitor UBO-QIC but not by the PKA inhibitor H89. Moreover, the results of Ala-scanning mutagenesis of hNPS-(1-13) indicated that residues Lys(11)and Lys(12)are structurally crucial for the hNPS receptor to couple to Gαs-dependent signaling. In conclusion, our findings demonstrate that hNPS-(1-10) is a biased agonist favoring Gαq-dependent signaling. It may represent a valuable chemical probe for further investigation of the therapeutic potential of human NPS receptor-directed signalingin vivo.
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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.