ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2003
Excitatory effects of orexin-A on nucleus tractus solitarius neurons are mediated by phospholipase C and protein kinase C.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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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
24 citing papers in PubMed, 87 citations in OpenAlex.
- The orexin system as a pharmacological target in inflammation: peripheral mechanisms and safety implications.Frontiers in pharmacology · 2026Review
- Signal transduction, dimerization, and therapeutic targeting of Orexin and receptor systems.Frontiers in pharmacology · 2025Review
- Altered ventilatory responses to hypercapnia-hypoxia challenges in a preclinical SUDEP model involve orexin neurons.Neurobiology of disease · 2024Article
- Orexin Facilitates the Peripheral Chemoreflex via Corticotropin-Releasing Hormone Neurons Projecting to the Nucleus of the Solitary Tract.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Timekeeping in the hindbrain: a multi-oscillatory circadian centre in the mouse dorsal vagal complex.Communications biology · 2020Article
- PKC inhibitor reversed the suppressive effect of orexin-A on IPSCs of locus coeruleus neurons in naloxone-induced morphine withdrawal.Journal of neural transmission (Vienna, Austria : 1996) · 2019Article
- Orexins and stress.Frontiers in neuroendocrinology · 2018Review
- Orexin Depolarizes Central Amygdala Neurons via Orexin Receptor 1, Phospholipase C and Sodium-Calcium Exchanger and Modulates Conditioned Fear.Frontiers in neuroscience · 2018Article
- Implicating the potential role of orexin in hypertension.Naunyn-Schmiedeberg's archives of pharmacology · 2017Review
- Role of the Orexin/Hypocretin System in Stress-Related Psychiatric Disorders.Current topics in behavioral neurosciences · 2017Review
- The Neurobiology of Sleep and Wakefulness.The Psychiatric clinics of North America · 2015Review
- Upregulation of orexin receptor in paraventricular nucleus promotes sympathetic outflow in obese Zucker rats.Neuropharmacology · 2015Article
- Calcium affects OX1 orexin (hypocretin) receptor responses by modifying both orexin binding and the signal transduction machinery.British journal of pharmacology · 2014Article
- Orexin/hypocretin receptor signalling: a functional perspective.British journal of pharmacology · 2014Article
- Orexin/hypocretin receptor signalling cascades.British journal of pharmacology · 2014Review
- Cannabinoid-hypocretin cross-talk in the central nervous system: what we know so far.Frontiers in neuroscience · 2013Review
- Orexin-A induces anxiety-like behavior through interactions with glutamatergic receptors in the bed nucleus of the stria terminalis of rats.Physiology & behavior · 2012Article
- Yohimbine depresses excitatory transmission in BNST and impairs extinction of cocaine place preference through orexin-dependent, norepinephrine-independent processes.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2012Article
- Orexin, stress, and anxiety/panic states.Progress in brain research · 2012Review
- Hypocretin-1 potentiates NMDA receptor-mediated somatodendritic secretion from locus ceruleus neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2008Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Orexin (ORX)-A is a 33-amino acid peptide with demonstrated roles in the regulation of energy metabolism, autonomic control, and sleep. Orexin receptors (OXRs), OX1R and OX2R, and immunoreactive axons are present in the nucleus tractus solitarius (NTS). We demonstrated previously that bath application of ORX-A depolarizes NTS neurons through activation of a nonselective cationic conductance (NSCC) and inhibition of a sustained potassium current (IK). The present study examined the signaling pathways underlying the excitatory effects of ORX-A on NTS neurons using whole-cell patch-clamp recording techniques. Inclusion of guanosine 5'-O-(2-thiodiphosphate) in the internal pipette solution abolished the effects of ORX-A, confirming that the actions of ORX-A are mediated by G-protein-coupled receptors. The responses of ORX-A were also blocked by a phospholipase C (PLC) inhibitor, D609, and by a nonselective protein kinase (PK) inhibitor, H7, demonstrating the involvement of PLC and protein kinases. However, PKA appears not to play a role, because the depolarizing effects of ORX-A were still observed when the PKA inhibitor peptide (6-22) was included in the pipette solution, and bath application of 8-bromo-cAMP (a PKA agonist) was without effect on NTS neurons. In contrast, 12-O-tetradecanoylphorbol-13-acetate (a PKC agonist) depolarized NTS neurons, and bisindolylmaleimide (BIS), a PKC inhibitor, abolished the depolarizing effects of ORX-A. Finally, voltage-clamp experiments demonstrated that BIS also blocked the activation of NSCC and inhibition of IK by ORX-A in NTS neurons. These results therefore show that the excitatory effects of ORX-A on NTS neurons are mediated through activation of the PLC-PKC-NSCC and -IK signaling pathways, which probably result from OXR-coupled activation of Gq.
Indexed as
Identifiers
12867505PMC6740536W1915837588What OpenQuestion holds
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.