ArticlePloS one2015
Constitutive Activity among Orphan Class-A G Protein Coupled Receptors.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 1 of them a synthesis that pooled it.
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Who cites it
91 citing papers in PubMed, 1 synthesis or guideline pooled it, 148 citations in OpenAlex.
- GPR3 in neuro-metabolic-immune-reproductive nexus - a potential therapeutic target for Multi-System diseases.Annals of medicine · 2026Pooled it
- GPR35 Mediates the Proliferation and Adipogenesis of Goat Intramuscular Preadipocytes Through the cAMP/PKA Signaling Pathway.Animals : an open access journal from MDPI · 2026Article
- Discovery of Small Molecule Ligands Targeting Orphan G Protein-Coupled Receptors GPR3, GPR6, and GPR12.Journal of medicinal chemistry · 2026Review
- International Union of Basic and Clinical Pharmacology. CXXII. Applying an objective evaluation to the status of class A orphan G protein-coupled receptors.Pharmacological reviews · 2026Review
- Mechanisms of Pertussis Toxin Action: ADP-Ribosylation and Its Role in Pertussis Pathogenesis.Toxins · 2026Review
- Peptide-functionalized nanoparticles for brain-targeted therapeutics.Drug delivery and translational research · 2026Review
- Constitutive activity among orphan G protein-coupled receptors: Molecular mechanisms and pharmacological perspectives.Molecular pharmacology · 2026Review
- GPCRs interaction with LGR5: Implications to cancer stemness.Journal of Cancer · 2026Article
- GPR25 promotes the formation of lung and liver tissue-resident memory CD8 T cells.Science immunology · 2025Article
- Gpr176 modulates the firing pattern of parvalbumin-positive interneurons in the orbitofrontal cortex of mouse.Molecular brain · 2025Article
- Comparing models and experimental structures of the GPR101 receptor: Artificial intelligence yields highly accurate models.Journal of molecular graphics & modelling · 2025Article
- Constitutive arrestin recruitment by orphan GPR52 via an atypical binding mode.Cell research · 2025Article
- G Protein-Coupled Receptor Signaling: Implications and Therapeutic Development Advances in Cancers.MedComm · 2025Review
- Constitutively active orphan G protein-coupled receptors through the lenses of cryo-electron microscopy.The Journal of biological chemistry · 2025Review
- Uncovering the role of Gpr45 in obesity regulation.Molecular metabolism · 2025Article
- Loss of G-protein coupled receptor 68 in hematopoietic tissues enhances long-term hematopoietic stem cell function upon aging.Stem cell research & therapy · 2025Article
- Orphan receptor GPR153 facilitates vascular damage responses by modulating cAMP levels, YAP/TAZ signaling, and NF-κB activation.Nature communications · 2025Article
- Complex G-protein signaling of the adhesion GPCR, ADGRA3.The Journal of biological chemistry · 2025Article
- The path of GPR87: from a P2Y-like receptor to its role in cancer progression.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Exploring the constitutive activation mechanism of the class A orphan GPR20.Acta pharmacologica Sinica · 2025Article
31 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The purpose of this study was to evaluate the extent of constitutive activity among orphan class-A G protein coupled receptors within the cAMP signaling pathway. Constitutive signaling was revealed by changes in gene expression under control of the cAMP response element. Gene expression was measured in Chinese hamster ovary cells transiently co-transfected with plasmids containing a luciferase reporter and orphan receptor. Criteria adopted for defining constitutive activation were: 1) 200% elevation over baseline reporter gene expression; 2) 40% inhibition of baseline expression; and 3) 40% inhibition of expression stimulated by 3 μM forskolin. Five patterns of activity were noted: 1) inhibition under both baseline and forskolin stimulated expression (GPR15, GPR17, GPR18, GPR20, GPR25, GPR27, GPR31, GPR32, GPR45, GPR57, GPR68, GPR83, GPR84, GPR132, GPR150, GPR176); 2) no effect on baseline expression, but inhibition of forskolin stimulated expression (GPR4, GPR26, GPR61, GPR62, GPR78, GPR101, GPR119); 3) elevation of baseline signaling coupled with inhibition of forskolin stimulated expression (GPR6, GPR12); 4) elevation of baseline signaling without inhibition of forskolin stimulated expression (GPR3, GPR21, GPR52, GPR65); and 5) no effect on expression (GPR1, GPR19, GPR22, GPR34, GPR35, GPR39, GPR63, GPR82, GPR85, GPR87). Constitutive activity was observed in 75% of the orphan class-A receptors examined (30 of 40). This constitutive signaling cannot be explained by simple overexpression of the receptor. Inhibition of cAMP mediated expression was far more common (65%) than stimulation of expression (15%). Orphan receptors that were closely related based on amino acid homology tended to have similar effects on gene expression. These results suggest that identification of inverse agonists may be a fruitful approach for categorizing these orphan receptors and targeting them for pharmacological intervention.
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