ArticleBritish journal of pharmacology2014
Pathway-selective antagonism of proteinase activated receptor 2.
Article in British journal of pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- Characterization and Functions of Protease-Activated Receptor 2 in Obesity, Diabetes, and Metabolic Syndrome: A Systematic Review.BioMed research international · 2016Pooled it
- MMP1 and PRSS23 induce PARCommunications biology · 2026Article
- Protease-Activated Receptor-2 Promotes Metastasis: An Emerging Therapeutic Target.Molecular cancer research : MCR · 2026Review
- Inhibition of protease-activated receptor-2 attenuates multi-walled carbon nanotube exacerbation of allergic lung disease in mice.Particle and fibre toxicology · 2025Article
- Structural basis for the activation of proteinase-activated receptors PAR1 and PAR2.Nature communications · 2025Article
- Prognostic Protein Biomarker Screening for Thyroid Carcinoma Based on Cancer Proteomics Profiles.Biomedicines · 2024Article
- GRespiratory research · 2024Review
- Genome editing ofActa pharmaceutica Sinica. B · 2024Article
- Protease-Activated Receptor 2 in inflammatory skin disease: current evidence and future perspectives.Frontiers in immunology · 2024Review
- Article
- PAR2 activation on human tubular epithelial cells engages converging signaling pathways to induce an inflammatory and fibrotic milieu.Frontiers in pharmacology · 2024Article
- Protease-activated receptor 2 attenuates doxorubicin-induced apoptosis in colon cancer cells.Journal of cell communication and signaling · 2023Article
- Tissue factor (coagulation factor III): a potential double-edge molecule to be targeted and re-targeted toward cancer.Biomarker research · 2023Review
- PARs in the inflammation-cancer transformation of CRC.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Review
- C781, a β-Arrestin Biased Antagonist at Protease-Activated Receptor-2 (PAR2), Displays in vivo Efficacy Against Protease-Induced Pain in Mice.The journal of pain · 2023Article
- Protease-activated receptors in health and disease.Physiological reviews · 2023Review
- GB83, an Agonist of PAR2 with a Unique Mechanism of Action Distinct from Trypsin and PAR2-AP.International journal of molecular sciences · 2022Article
- PAR2-Induced Tissue Factor Synthesis by Primary Cultures of Human Kidney Tubular Epithelial Cells Is Modified by Glucose Availability.International journal of molecular sciences · 2021Article
- Legumain Induces Oral Cancer Pain by Biased Agonism of Protease-Activated Receptor-2.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- PAR2 Activation on Human Kidney Tubular Epithelial Cells Induces Tissue Factor Synthesis, That Enhances Blood Clotting.Frontiers in physiology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeProteinase activated receptor 2 (PAR2) is a GPCR associated with inflammation, metabolism and disease. Clues to understanding how to block PAR2 signalling associated with disease without inhibiting PAR2 activation in normal physiology could be provided by studies of biased signalling. EXPERIMENTAL APPROACH: PAR2 ligand GB88 was profiled for PAR2 agonist and antagonist properties by several functional assays associated with intracellular G-protein-coupled signalling in vitro in three cell types and with PAR2-induced rat paw oedema in vivo. KEY
resultsIn HT29 cells, GB88 was a PAR2 antagonist in terms of Ca(2+) mobilization and PKC phosphorylation, but a PAR2 agonist in attenuating forskolin-induced cAMP accumulation, increasing ERK1/2 phosphorylation, RhoA activation, myosin phosphatase phosphorylation and actin filament rearrangement. In CHO-hPAR2 cells, GB88 inhibited Ca(2+) release, but activated G(i/o) and increased ERK1/2 phosphorylation. In human kidney tubule cells, GB88 inhibited cytokine secretion (IL6, IL8, GM-CSF, TNF-α) mediated by PAR2. A rat paw oedema induced by PAR2 agonists was also inhibited by orally administered GB88 and compared with effects of locally administered inhibitors of G-protein coupled pathways. CONCLUSIONS AND IMPLICATIONS: GB88 is a biased antagonist of PAR2 that selectively inhibits PAR2/G(q/11)/Ca(2+)/PKC signalling, leading to anti-inflammatory activity in vivo, while being an agonist in activating three other PAR2-activated pathways (cAMP, ERK, Rho) in human cells. These findings highlight opportunities to design drugs to block specific PAR2-linked signalling pathways in disease, without blocking beneficial PAR2 signalling in normal physiology, and to dissect PAR2-associated mechanisms of disease in vivo.
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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.