ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2014
Transmembrane peptides as unique tools to demonstrate the in vivo action of a cross-class GPCR heterocomplex.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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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.
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Who cites it
27 citing papers in PubMed, 50 citations in OpenAlex.
- Small molecule inhibitor of orphan GPCR dimerization improves host defense and blood pressure control in mice.The Journal of clinical investigation · 2026Article
- Mechanistic and therapeutic insights into class A GPCR dimers in neuropsychiatric disorders.npj drug discovery · 2026Review
- GPCR Heterodimers: Implications for Biased Signaling.Handbook of experimental pharmacology · 2026Review
- β2-Adrenergic Receptor Utilizes Distinct Interaction Interfaces to Selectively form Heterooligomers with a Subset of Bitter Taste Receptors.Biochemistry · 2025Article
- Orphan G protein-coupled receptor GPRC5B controls macrophage function by facilitating prostaglandin E receptor 2 signaling.Nature communications · 2025Article
- RNA therapeutics in targeting G protein-coupled receptors: Recent advances and challenges.Molecular therapy. Nucleic acids · 2024Review
- The histamine H3 receptor modulates dopamine D2 receptor-dependent signaling pathways and mouse behaviors.The Journal of biological chemistry · 2023Article
- Small Activating RNA Modulation of the G Protein-Coupled Receptor for Cancer Treatment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Disrupting GPCR Complexes with Smart Drug-like Peptides.Pharmaceutics · 2022Review
- Central regulation of body fluid homeostasis.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2022Review
- Probing GPCR Dimerization Using Peptides.Frontiers in endocrinology · 2022Review
- Angiotensin and Endothelin Receptor Structures With Implications for Signaling Regulation and Pharmacological Targeting.Frontiers in endocrinology · 2022Review
- Modulation of dopamine DeLife · 2020Article
- Structural Basis for Allosteric Modulation of Class B G Protein-Coupled Receptors.Annual review of pharmacology and toxicology · 2020Review
- Design and development of stapled transmembrane peptides that disrupt the activity of G-protein-coupled receptor oligomers.The Journal of biological chemistry · 2019Article
- Distribution and Functional Implication of Secretin in Multiple Brain Regions.Journal of molecular neuroscience : MN · 2019Review
- Article
- Singular Location and Signaling Profile of Adenosine ANeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Article
- Mapping the Interface of a GPCR Dimer: A Structural Model of the AFrontiers in pharmacology · 2018Article
- Differential Contribution of Transmembrane Domains IV, V, VI, and VII to Human Angiotensin II Type 1 Receptor Homomer Formation.The Journal of biological chemistry · 2017Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Angiotensin (ANGII) and secretin (SCT) share overlapping, interdependent osmoregulatory functions in brain, where SCT peptide/receptor function is required for ANGII action, yet the molecular basis is unknown. Since receptors for these peptides (AT1aR, SCTR) are coexpressed in osmoregulatory centers, a possible mechanism is formation of a cross-class receptor heterocomplex. Here, we demonstrate such a complex and its functional importance to modulate signaling. Association of AT1aR with SCTR reduced ability of SCT to stimulate cyclic adenosine monophosphate (cAMP), with signaling augmented in presence of ANGII or constitutively active AT1aR. Several transmembrane (TM) peptides of these receptors were able to affect their conformation within complexes, reducing receptor BRET signals. AT1aR TM1 affected only formation and activity of the heterocomplex, without effect on homomers of either receptor, and reduced SCT-stimulated cAMP responses in cells expressing both receptors. This peptide was active in vivo by injection into mouse lateral ventricle, thereby suppressing water-drinking behavior after hyperosmotic shock, similar to SCTR knockouts. This supports the interpretation that active conformation of AT1aR is a key modulator of cAMP responses induced by SCT stimulation of SCTR. The SCTR/AT1aR complex is physiologically important, providing differential signaling to SCT in settings of hyperosmolality or food intake, modulated by differences in levels of ANGII.
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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.