ArticleBritish journal of pharmacology2012
OX1 orexin/hypocretin receptor activation of phospholipase D.
Article in British journal of pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 40 citations in OpenAlex.
- Choline-An Essential Nutrient with Health Benefits and a Signaling Molecule.International journal of molecular sciences · 2025Review
- Signal transduction, dimerization, and therapeutic targeting of Orexin and receptor systems.Frontiers in pharmacology · 2025Review
- Orexin Signaling: A Complex, Multifaceted Process.Frontiers in cellular neuroscience · 2022Review
- Identification and Characterization of Cannabidiol as an OX1R Antagonist by Computational and In Vitro Functional Validation.Biomolecules · 2021Article
- Choline-Sigma-1R as an Additional Mechanism for Potentiation of Orexin by Cocaine.International journal of molecular sciences · 2021Article
- Orexin receptors in GtoPdb v.2021.3.IUPHAR/BPS guide to pharmacology CITE · 2021Article
- Treatment with Gold Nanoparticles UsingInternational journal of molecular sciences · 2020Article
- The auxiliary subunit KCNE1 regulates KCNQ1 channel response to sustained calcium-dependent PKC activation.PloS one · 2020Article
- Fluvastatin inhibits Rab5-mediated IKs internalization caused by chronic CaJournal of molecular and cellular cardiology · 2019Article
- The Orexin/Receptor System: Molecular Mechanism and Therapeutic Potential for Neurological Diseases.Frontiers in molecular neuroscience · 2018Review
- Comparative Network Analysis of Patients with Non-Small Cell Lung Cancer and Smokers for Representing Potential Therapeutic Targets.Scientific reports · 2017Article
- Global analysis of gene expression mediated by OX1 orexin receptor signaling in a hypothalamic cell line.PloS one · 2017Article
- Orexin receptor agonist Yan 7874 is a weak agonist of orexin/hypocretin receptors and shows orexin receptor-independent cytotoxicity.PloS one · 2017Article
- Calcium affects OX1 orexin (hypocretin) receptor responses by modifying both orexin binding and the signal transduction machinery.British journal of pharmacology · 2014Article
- Orexin/hypocretin based pharmacotherapies for the treatment of addiction: DORA or SORA?CNS drugs · 2014Review
- Orexin/hypocretin receptor signalling: a functional perspective.British journal of pharmacology · 2014Article
- Orexin/hypocretin receptor signalling cascades.British journal of pharmacology · 2014Review
- Orexin/Hypocretin Signaling.Current topics in behavioral neurosciencesReview
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
background and purposeOrexin receptors potently signal to lipid messenger systems, and our previous studies have suggested that PLD would be one of these. We thus wanted to verify this by direct measurements and clarify the molecular mechanism of the coupling. EXPERIMENTAL APPROACH: Orexin receptor-mediated PLD activation was investigated in CHO cells stably expressing human OX(1) orexin receptors using [(14) C]-oleic acid-prelabelling and the transphosphatidylation assay. KEY
resultsOrexin stimulation strongly increased PLD activity - even more so than the phorbol ester TPA (12-O-tetradecanoyl-phorbol-13-acetate), a highly potent activator of PLD. Both orexin and TPA responses were mediated by PLD1. Orexin-A and -B showed approximately 10-fold difference in potency, and the concentration-response curves were biphasic. Using pharmacological inhibitors and activators, both orexin and TPA were shown to signal to PLD1 via the novel PKC isoform, PKCδ. In contrast, pharmacological or molecular biological inhibitors of Rho family proteins RhoA/B/C, cdc42 and Rac did not inhibit the orexin (or the TPA) response, nor did the molecular biological inhibitors of PKD. In addition, neither cAMP elevation, Gα(i/o) nor Gβγ seemed to play an important role in the orexin response. CONCLUSIONS AND IMPLICATIONS: Stimulation of OX(1) receptors potently activates PLD (probably PLD1) in CHO cells and this is mediated by PKCδ but not other PKC isoforms, PKDs or Rho family G-proteins. At present, the physiological significance of orexin-induced PLD activation is unknown, but this is not the first time we have identified PKCδ in orexin signalling, and thus some specific signalling cascade may exist between orexin receptors and PKCδ.
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Registered trials
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