ArticleThe Journal of pharmacology and experimental therapeutics2016
Central GPR109A Activation Mediates Glutamate-Dependent Pressor Response in Conscious Rats.
Article in The Journal of pharmacology and experimental therapeutics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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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
22 citing papers in PubMed, 32 citations in OpenAlex.
- The immune-microbiome axis in salt-sensitive hypertension: a focus on renal and neural mechanisms.Frontiers in physiology · 2025Review
- Association of dietary niacin intake with all-cause mortality in chronic kidney disease: A retrospective cohort study of NHANES.PloS one · 2025Article
- The gut microbiota in high-altitude medicine: intersection of hypoxic adaptation and disease management.Frontiers in microbiology · 2025Review
- Dual COX-2 and 15-LOX inhibition study of novel 4-arylidine-2-mercapto-1-phenyl-1H-imidazolidin-5(4H)-ones: Design, synthesis, docking, and anti-inflammatory activity.Archiv der Pharmazie · 2024Article
- Metabolite signaling in the heart.Nature cardiovascular research · 2023Review
- Emerging roles of GPR109A in regulation of neuroinflammation in neurological diseases and pain.Neural regeneration research · 2023Review
- Short-Chain Fatty Acid Receptors and Blood Pressure Regulation: Council on Hypertension Mid-Career Award for Research Excellence 2021.Hypertension (Dallas, Tex. : 1979) · 2022Review
- Central and peripheral regulations mediated by short-chain fatty acids on energy homeostasis.Translational research : the journal of laboratory and clinical medicine · 2022Review
- Neuroprotective effects of dimethyl fumarate against depression-like behaviors via astrocytes and microglia modulation in mice: possible involvement of the HCAR2/Nrf2 signaling pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2022Article
- Design and Synthesis of Novel 1,3,4-Oxadiazole and 1,2,4-Triazole Derivatives as Cyclooxygenase-2 Inhibitors with Anti-inflammatory and Antioxidant activity in LPS-stimulated RAW264.7 Macrophages.Bioorganic chemistry · 2022Article
- Article
- β-Hydroxybutyrate in Cardiovascular Diseases : A Minor Metabolite of Great Expectations.Frontiers in molecular biosciences · 2022Review
- Design and synthesis of novel quinazolinones conjugated ibuprofen, indole acetamide, or thioacetohydrazide as selective COX-2 inhibitors: anti-inflammatory, analgesic and anticancer activities.Journal of enzyme inhibition and medicinal chemistry · 2021Article
- Novel 1,2,4-triazine-quinoline hybrids: The privileged scaffolds as potent multi-target inhibitors of LPS-induced inflammatory response via dual COX-2 and 15-LOX inhibition.European journal of medicinal chemistry · 2021Article
- Beneficial Effects of Exogenous Ketogenic Supplements on Aging Processes and Age-Related Neurodegenerative Diseases.Nutrients · 2021Review
- Cardioprotecive Properties of Known Agents in Rat Ischemia-Reperfusion Model Under Clinically Relevant Conditions: Only the NAD Precursor Nicotinamide Riboside Reduces Infarct Size in Presence of Fentanyl, Midazolam and Cangrelor, but Not Propofol.Frontiers in cardiovascular medicine · 2021Article
- Short-Chain Fatty Acids and Their Association with Signalling Pathways in Inflammation, Glucose and Lipid Metabolism.International journal of molecular sciences · 2020Review
- Gut Microbial Metabolites and Blood Pressure Regulation: Focus on SCFAs and TMAO.Physiology (Bethesda, Md.) · 2020Review
- Role of Short Chain Fatty Acid Receptors in Intestinal Physiology and Pathophysiology.Comprehensive Physiology · 2018Review
- β-Hydroxybutyrate: A Signaling Metabolite.Annual review of nutrition · 2017Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
G protein-coupled receptor 109A (GPR109A) activation by its ligand nicotinic acid (NA) in immune cells increases Ca(2+) levels, and Ca(2+) induces glutamate release and oxidative stress in central blood pressure (BP)-regulating nuclei, for example, the rostral ventrolateral medulla (RVLM), leading to sympathoexcitation. Despite NA's ability to reach the brain, the expression and function of its receptor GPR109A in the RVLM remain unknown. We hypothesized that NA activation of RVLM GPR109A causes Ca(2+)-dependent l-glutamate release and subsequently increases neuronal oxidative stress, sympathetic activity, and BP. To test this hypothesis, we adopted a multilevel approach, which included pharmacologic in vivo studies along with ex vivo and in vitro molecular studies in rat pheochromocytoma cell line (PC12) cells (which exhibit neuronal phenotype). We present the first evidence for GPR109A expression in the RVLM and in PC12 cells. Next, we showed that RVLM GPR109A activation (NA) caused pressor and bradycardic responses in conscious rats. The resemblance of these responses to those caused by intra-RVLM glutamate and their attenuation by NMDA receptor (NMDAR) blockade (2-amino-5-phosphonopentanoic acid) and enhancement by l-glutamate uptake inhibition (l-trans-pyrrolidine-2,4-dicarboxylic acid, PDC) supported our hypothesis. NA increased Ca(2+), glutamate, nitric oxide and reactive oxygen species (ROS) levels in PC12 cells and increased RVLM ROS levels. The inactive NA analog isonicotinic acid failed to replicate the cardiovascular and biochemical effects of NA. Further, GPR109A knockdown (siRNA) abrogated the biochemical effects of NA in PC12 cells. These novel findings yield new insight into the role of RVLM GPR109A in central BP control.
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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.