ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2017
Protamine is an antagonist of apelin receptor, and its activity is reversed by heparin.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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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
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Cationic Arginine-Rich Peptides (CARPs): A Novel Class of Neuroprotective Agents With a Multimodal Mechanism of Action.Frontiers in neurology · 2020Pooled it
- International Union of Basic and Clinical Pharmacology. CXXI. Apelin receptor pharmacology in the human cardiovascular system and emerging clinical applications.Pharmacological reviews · 2026Review
- The Apelinergic System in Kidney Disease: Novel Perspectives.International journal of molecular sciences · 2025Review
- Apelin/APJ: Another Player in the Cancer Biology Network.International journal of molecular sciences · 2025Review
- CXCL17 is an allosteric inhibitor of CXCR4 through a mechanism of action involving glycosaminoglycans.Science signaling · 2024Article
- Protamine as a barrier against the angiogenic effect of insulin: a possible role of apelin.Scientific reports · 2023Article
- GPCR in Adipose Tissue Function-Focus on Lipolysis.Biomedicines · 2023Review
- MicroRNA-631 Resensitizes Doxorubicin-Resistant Chondrosarcoma Cells by Targeting Apelin.International journal of molecular sciences · 2023Article
- Intravenous thrombolysis in acute ischemic stroke after antagonization of unfractionated heparin with protamine: case series and systematic review of literature.Therapeutic advances in neurological disorders · 2023Article
- Upregulated Apelin Signaling in Pancreatic Cancer Activates Oncogenic Signaling Pathways to Promote Tumor Development.International journal of molecular sciences · 2022Article
- Prognostic roles of diabetes mellitus and hypertension in advanced hepatocellular carcinoma treated with sorafenib.PloS one · 2020Article
- The apelinergic system: a perspective on challenges and opportunities in cardiovascular and metabolic disorders.Annals of the New York Academy of Sciences · 2019Review
- International Union of Basic and Clinical Pharmacology. CVII. Structure and Pharmacology of the Apelin Receptor with a Recommendation that Elabela/Toddler Is a Second Endogenous Peptide Ligand.Pharmacological reviews · 2019Review
- Apelin/APJ system: A potential therapeutic target for endothelial dysfunction-related diseases.Journal of cellular physiology · 2019Review
- A novel cyclic biased agonist of the apelin receptor, MM07, is disease modifying in the rat monocrotaline model of pulmonary arterial hypertension.British journal of pharmacology · 2019Article
- Perinatal Hypoxic-Ischemic Encephalopathy and Neuroprotective Peptide Therapies: A Case for Cationic Arginine-Rich Peptides (CARPs).Brain sciences · 2018Review
- Adipose Tissue Metabolism and Cancer Progression: Novel Insights from Gut Microbiota?Current pathobiology reports · 2017Review
Corrections and comments
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Authors and funding
15 authors at 7 institutions in 2 countries.
Funding
Abstract
Apelin signaling plays an important role during embryo development and regulates angiogenesis, cardiovascular activity, and energy metabolism in adulthood. Overexpression and hyperactivity of this signaling pathway is observed in various pathologic states, such as cardiovascular diseases and cancer, which highlights the importance of inhibiting apelin receptor (APJ); therefore, we developed a cell-based screening assay that uses fluorescence microscopy to identify APJ antagonists. This approach led us to identify the U.S. Food and Drug Administration-approved compound protamine-already used clinically after cardiac surgery-as an agent to bind to heparin and thereby reverse its anticlotting activity. Protamine displays a 390-nM affinity for APJ and behaves as a full antagonist with regard to G protein and β-arrestin-dependent intracellular signaling.
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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.