ArticleTranslational psychiatry2022
Disruption of 5-hydroxytryptamine 1A receptor and orexin receptor 1 heterodimer formation affects novel G protein-dependent signaling pathways and has antidepressant effects in vivo.
Article in Translational psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 19 citations in OpenAlex.
- Moderate-intensity treadmill exercise improved the anticonvulsant efficacy of topiramate and attenuated anxiety and depressive-like side effects in epileptic rats by upregulating 5-HT1A receptors in the hippocampus and cerebral cortex.IBRO neuroscience reports · 2026Article
- Novel anxiolytic-antidepressant combinations TF-1 and TF-2 and their intervention mechanisms in a mouse model of comorbid anxiety and depression (CAD).Frontiers in pharmacology · 2026Article
- GPCR Heterodimers: Implications for Biased Signaling.Handbook of experimental pharmacology · 2026Review
- The orexin system as a pharmacological target in inflammation: peripheral mechanisms and safety implications.Frontiers in pharmacology · 2026Review
- The Orexin System in Addiction: Neuromodulatory Interactions and Therapeutic Potential.Brain sciences · 2025Review
- Single-molecule localization microscopy as a tool to quantify di/oligomerization of receptor tyrosine kinases and G protein-coupled receptors.Molecular pharmacology · 2025Review
- Signal transduction, dimerization, and therapeutic targeting of Orexin and receptor systems.Frontiers in pharmacology · 2025Review
- MicroRNAs as Regulators of Neuroinflammation in Major Depressive Disorder.Depression and anxiety · 2025Review
- Hypocretin-1/Hypocretin Receptor 1 Regulates Neuroplasticity and Cognitive Function through Hippocampal Lactate Homeostasis in Depressed Model.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Unraveling the Mechanisms of Cannabidiol's Pharmacological Actions: A Comprehensive Research Overview.Topics in current chemistry (Cham) · 2024Review
- Functional Dimerization of Serotonin Receptors: Role in Health and Depressive Disorders.International journal of molecular sciences · 2023Review
- The World of GPCR dimers - Mapping dopamine receptor DComputational and structural biotechnology journal · 2023Article
- Potential of Heterogeneous Compounds as Antidepressants: A Narrative Review.International journal of molecular sciences · 2022Review
- Biology of cyclooxygenase-2: An application in depression therapeutics.Frontiers in psychiatry · 2022Review
Corrections and comments
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Authors and funding
18 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
G protein-coupled receptor (GPCR) heterodimers are new targets for the treatment of depression. Increasing evidence supports the importance of serotonergic and orexin-producing neurons in numerous physiological processes, possibly via a crucial interaction between 5-hydroxytryptamine 1A receptor (5-HT1AR) and orexin receptor 1 (OX1R). However, little is known about the function of 5-HT1AR/OX1R heterodimers. It is unclear how the transmembrane domains (TMs) of the dimer affect its function and whether its modulation mediates antidepressant-like effects. Here, we examined the mechanism of 5-HT1AR/OX1R dimerization and downstream G protein-dependent signaling. We found that 5-HT1AR and OX1R form constitutive heterodimers that induce novel G protein-dependent signaling, and that this heterodimerization does not affect recruitment of β-arrestins to the complex. In addition, we found that the structural interface of the active 5-HT1AR/OX1R dimer transforms from TM4/TM5 in the basal state to TM6 in the active conformation. We also used mutation analyses to identify key residues at the interface (5-HT1AR R151
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