ArticleInternational journal of molecular sciences2017
NPFFR2 Activates the HPA Axis and Induces Anxiogenic Effects in Rodents.
Article in International journal of molecular sciences, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 31 citations in OpenAlex.
- The arginine-phenylalanine-amide neuropeptide receptor family: Physiological effects, drug development, and structural insights.Neural regeneration research · 2026Article
- Peptides from General By-Products: Unveiling Their Potential Biological Activities in Human Health.Molecules (Basel, Switzerland) · 2025Review
- Serum Neuropeptide FFR2 is increased in pregnant women with pre-eclampsia and associated with pregnancy outcomes.Pakistan journal of medical sciences · 2025Article
- An Overview on Renal and Central Regulation of Blood Pressure by Neuropeptide FF and Its Receptors.International journal of molecular sciences · 2024Review
- An Honest Reckoning With the Amygdala and Mental Illness.The American journal of psychiatry · 2024Review
- Review
- DNA methylation in cocaine use disorder-An epigenome-wide approach in the human prefrontal cortex.Frontiers in psychiatry · 2023Article
- Anxiety and Depression: What Do We Know of Neuropeptides?Behavioral sciences (Basel, Switzerland) · 2022Review
- NPFF Decreases Activity of Human Arcuate NPY Neurons: A Study in Embryonic-Stem-Cell-Derived Model.International journal of molecular sciences · 2022Article
- Article
- Transcriptomic Changes in Mouse Bone Marrow-Derived Macrophages Exposed to Neuropeptide FF.Genes · 2021Article
- Prognostic plasma exosomal microRNA biomarkers in patients with substance use disorders presenting comorbid with anxiety and depression.Scientific reports · 2021Article
- Elevated Serum Neuropeptide FF Levels Are Associated with Cognitive Decline in Patients with Spinal Cord Injury.Disease markers · 2021Article
- Article
- Neuropeptide FF and Its Receptors: Therapeutic Applications and Ligand Development.Journal of medicinal chemistry · 2020Article
- Identification of a 3-mRNA signature as a novel potential prognostic biomarker in patients with ovarian serous cystadenocarcinoma in G2 and G3.Oncology letters · 2019Article
- Role of the Hypothalamic-Pituitary-Adrenal Axis in Health and Disease.International journal of molecular sciences · 2018Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuropeptide FF (NPFF) belongs to the RFamide family and is known as a morphine-modulating peptide. NPFF regulates various hypothalamic functions through two receptors, NPFFR1 and NPFFR2. The hypothalamic-pituitary-adrenal (HPA) axis participates in physiological stress response by increasing circulating glucocorticoid levels and modulating emotional responses. Other RFamide peptides, including neuropeptide AF, neuropeptide SF and RFamide related peptide also target NPFFR1 or NPFFR2, and have been reported to activate the HPA axis and induce anxiety- or depression-like behaviors. However, little is known about the action of NPFF on HPA axis activity and anxiety-like behaviors, and the role of the individual receptors remains unclear. In this study, NPFFR2 agonists were used to examine the role of NPFFR2 in activating the HPA axis in rodents. Administration of NPFFR2 agonists, dNPA (intracerebroventricular, ICV) and AC-263093 (intraperitoneal, IP), time-dependently (in rats) and dose-dependently (in mice) increased serum corticosteroid levels and the effects were counteracted by the NPFF receptor antagonist, RF9 (ICV), as well as corticotropin-releasing factor (CRF) antagonist, α-helical CRF(9-41) (intravenous, IV). Treatment with NPFFR2 agonist (AC-263093, IP) increased c-Fos protein expression in the hypothalamic paraventricular nucleus and induced an anxiogenic effect, which was evaluated in mice using an elevated plus maze. These findings reveal, for the first time, that the direct action of hypothalamic NPFFR2 stimulates the HPA axis and triggers anxiety-like behaviors.
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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.