ArticleThe Journal of biological chemistry2009
Thrombin promotes release of ATP from lung epithelial cells through coordinated activation of rho- and Ca2+-dependent signaling pathways.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 106 citations in OpenAlex.
- Histamine induces ATP release from human subcutaneous fibroblasts, via pannexin-1 hemichannels, leading to Ca2+ mobilization and cell proliferation.The Journal of biological chemistry · 2013Trial
- Protease-activated receptors act as a liaison between metabolism and inflammation.Inflammopharmacology · 2026Review
- Differential Regulation of Hemichannels and Gap Junction Channels by RhoA GTPase and Actin Cytoskeleton: A Comparative Analysis of Cx43 and Cx26.International journal of molecular sciences · 2024Article
- Echinocystic acid induces the apoptosis, and inhibits the migration and invasion of non-small cell lung cancer cells.Medical oncology (Northwood, London, England) · 2023Article
- A novel definition and treatment of hyperinflammation in COVID-19 based on purinergic signalling.Purinergic signalling · 2022Review
- Deacetylation as a receptor-regulated direct activation switch for pannexin channels.Nature communications · 2021Article
- Airway Epithelial Nucleotide Release Contributes to Mucociliary Clearance.Life (Basel, Switzerland) · 2021Review
- Purinergic receptors in airway hydration.Biochemical pharmacology · 2021Review
- Emerging Roles of Protease-Activated Receptors (PARs) in the Modulation of Synaptic Transmission and Plasticity.International journal of molecular sciences · 2021Review
- Rhinovirus-16 increases ATP release in A549 cells without concomitant increase in production.ERJ open research · 2020Article
- Pannexin 1 channels in renin-expressing cells influence renin secretion and blood pressure homeostasis.Kidney international · 2020Article
- Article
- Analysis of purine receptor expression and functionality in alveolar epithelial cells.Purinergic signalling · 2020Article
- Constitutive SRC-mediated phosphorylation of pannexin 1 at tyrosine 198 occurs at the plasma membrane.The Journal of biological chemistry · 2019Article
- Pannexin-1 in Human Lymphatic Endothelial Cells Regulates Lymphangiogenesis.International journal of molecular sciences · 2018Article
- ATP Release Channels.International journal of molecular sciences · 2018Review
- Revisiting multimodal activation and channel properties of Pannexin 1.The Journal of general physiology · 2018Review
- Interactions of Pannexin1 channels with purinergic and NMDA receptor channels.Biochimica et biophysica acta. Biomembranes · 2018Review
- The Role of Gap Junction-Mediated Endothelial Cell-Cell Interaction in the Crosstalk between Inflammation and Blood Coagulation.International journal of molecular sciences · 2017Review
- A quantized mechanism for activation of pannexin channels.Nature communications · 2017Article
3 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Extracellular ATP controls key aspects of lung function via activation of epithelial cell purinergic receptors, but how ATP is released from cells remains poorly understood. To identify mechanistic components upstream of ATP release, we examined the effect of selected G protein coupled-receptor activation on ATP release from lung epithelial cells. The protease-activated receptor (PAR) agonist thrombin elicited a rapid Ca(2+)-dependent release of ATP from A549 cells. In contrast, the P2Y(2) receptor agonist UTP caused negligible ATP release, despite promoting a robust Ca(2+) response. Agonist-elicited ATP release was associated with Rho activation and was reduced in cells transfected with dominant negative mutants of p115-Rho GEF or RhoA, and by inhibitors of Rho kinase (ROCK). However, RhoA activation alone did not promote ATP release if temporally separated from Ca(2+) mobilization. PAR3 was the only PAR subtype detected in A549 cells by reverse transcription-PCR. Transfection of cells with human PAR3 cDNA increased thrombin-promoted ATP release, inositol phosphate formation, and RhoA activation. Conversely, small interference RNA against PAR3 diminished thrombin-evoked responses. Thrombin-elicited ATP release was accompanied by an enhanced cellular uptake of propidium iodide in a Ca(2+)- and ROCK-dependent manner and was inhibited by connexin/pannexin hemichannel blockers. Our data suggest that thrombin promotes ATP release from A549 cells via Rho- and Ca(2+)-dependent activation of connexin/pannexin hemichannels. The relevance of these findings is highlighted by the observation that exposure of primary cultures of well differentiated human bronchial epithelial cells to thrombin resulted in robust ATP release, which was inhibited by ROCK inhibitors and by connexin/pannexin hemichannel blockers.
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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.