ArticleBritish journal of pharmacology2012
Intermedin (adrenomedullin2) stabilizes the endothelial barrier and antagonizes thrombin-induced barrier failure in endothelial cell monolayers.
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 37 papers.
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Who cites it
37 citing papers in PubMed, 58 citations in OpenAlex.
- Role of exchange proteins directly activated by cAMP signaling in vascular remodeling.Pharmacological reviews · 2025Review
- Adrenomedullin 2 attenuates anxiety-like behaviors by increasing IGF-II in amygdala and re-establishing blood-brain barrier.Translational psychiatry · 2025Article
- IntermedinJournal of inflammation research · 2025Article
- Vascular leak in sepsis: physiological basis and potential therapeutic advances.Critical care (London, England) · 2024Review
- Adrenomedullin 2/intermedin is a slow off-rate, long-acting endogenous agonist of the adrenomedullinbioRxiv : the preprint server for biology · 2023Article
- ZNF185 prevents stress fiber formation through the inhibition of RhoA in endothelial cells.Communications biology · 2023Article
- Actin cytoskeleton in angiogenesis.Biology open · 2022Review
- Sustained Activation of CLR/RAMP Receptors by Gel-Forming Agonists.International journal of molecular sciences · 2022Article
- Vascular and Liver Homeostasis in Juvenile Mice Require Endothelial Cyclic AMP-Dependent Protein Kinase A.International journal of molecular sciences · 2022Article
- Somatostatin Primes Endothelial Cells for Agonist-Induced Hyperpermeability and Angiogenesis In Vitro.International journal of molecular sciences · 2022Article
- Review
- Gel-forming antagonist provides a lasting effect on CGRP-induced vasodilation.Frontiers in pharmacology · 2022Article
- PETN-Induced Antioxidative Properties in Endothelial Cells as a Target for Secondary Prevention of Endothelial Dysfunction in Pregnancy.Frontiers in physiology · 2022Article
- Molecular Dambusters: What Is Behind Hyperpermeability in Bradykinin-Mediated Angioedema?Clinical reviews in allergy & immunology · 2021Review
- Article
- Intermedin facilitates hepatocellular carcinoma cell survival and invasion via ERK1/2-EGR1/DDIT3 signaling cascade.Scientific reports · 2021Article
- Article
- K-134, a phosphodiesterase 3 inhibitor, reduces vascular inflammation and hypoxia, and prevents rupture of experimental abdominal aortic aneurysms.JVS-vascular science · 2020Article
- Inhibition of Protein Prenylation of GTPases Alters Endothelial Barrier Function.International journal of molecular sciences · 2019Article
- The novel exchange protein activated by cyclic AMP 1 (EPAC1) agonist, I942, regulates inflammatory gene expression in human umbilical vascular endothelial cells (HUVECs).Biochimica et biophysica acta. Molecular cell research · 2019Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeIntermedin is a member of the calcitonin gene-related-peptide (CGRP) family expressed in endothelial cells and acts via calcitonin receptor-like receptors (CLRs). Here we have analysed the receptors for intermedin and its effect on the endothelial barrier in monolayers of human umbilical vein endothelial cells (HUVECs). EXPERIMENTAL APPROACH: We analysed the effect of intermedin on albumin permeability, contractile machinery, actin cytoskeleton and VE-cadherin in cultured HUVECs. KEY
resultsIntermedin concentration-dependently reduced basal endothelial permeability to albumin and antagonized thrombin-induced hyperpermeability. Intermedin was less potent (EC(50) 1.29 ± 0.12 nM) than adrenomedullin (EC(50) 0.24 ± 0.07 nM) in reducing endothelial permeability. These intermedin effects were inhibited by AM(22-52) and higher concentrations of αCGRP(8-37), with pA(2) values of αCGRP(8-37) of 6.4 for both intermedin and adrenomedullin. PCR data showed that HUVEC expressed only the CLR/RAMP2 receptor complex. Intermedin activated cAMP/PKA and cAMP/Epac signalling pathways. Intermedin's effect on permeability was blocked by inhibition of PKA but not of eNOS. Intermedin antagonized thrombin-induced contractile activation, RhoA activation and stress fibre formation. It also induced Rac1 activation, enhanced cell-cell adhesion and antagonized thrombin-induced loss of cell-cell adhesion. Treatment with a specific inhibitor of Rac1 prevented intermedin-mediated barrier stabilization. CONCLUSION AND IMPLICATIONS: Intermedin stabilized endothelial barriers in HUVEC monolayers via CLR/RAMP2 receptors. These effects were mediated via cAMP-mediated inactivation of contractility and strengthening of cell-cell adhesion. These findings identify intermedin as a barrier stabilizing agent and suggest intermedin as a potential treatment for vascular leakage in inflammatory conditions.
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