ArticleBritish journal of pharmacology2001
Agonists of proteinase-activated receptor 1 induce plasma extravasation by a neurogenic mechanism.
Article in British journal of pharmacology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 140 citations in OpenAlex.
- Neuronal substance P-driven MRGPRX2-dependent mast cell degranulation products differentially promote vascular permeability.Frontiers in immunology · 2024Article
- Article
- Construction of iron metabolism-related prognostic features of gastric cancer based on RNA sequencing and TCGA database.BMC cancer · 2023Article
- Thrombin Activity in Rodent and Human Skin: Modified by Inflammation and Correlates with Innervation.Biomedicines · 2022Article
- Neurokinin Receptor 1 (NK1R) Antagonist Aprepitant Enhances Hematoma Clearance by Regulating Microglial Polarization via PKC/p38MAPK/NFκB Pathway After Experimental Intracerebral Hemorrhage in Mice.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Article
- The transient receptor potential vanilloid 4 (TRPV4) ion channel mediates protease activated receptor 1 (PAR1)-induced vascular hyperpermeability.Laboratory investigation; a journal of technical methods and pathology · 2020Article
- Weisheng-Tang Ameliorates Acute Ischemic Brain Damage in Mice by Maintaining Blood-Brain Barrier Integrity.Oxidative medicine and cellular longevity · 2019Article
- MMP1/PAR1/SP/NK1R paracrine loop modulates early perineural invasion of pancreatic cancer cells.Theranostics · 2018Article
- Protease-Activated Receptor-1 Supports Locomotor Recovery by Biased Agonist Activated Protein C after Contusive Spinal Cord Injury.PloS one · 2017Article
- Protease-activated receptors in kidney disease progression.American journal of physiology. Renal physiology · 2016Review
- Urinary bladder hypersensitivity and dysfunction in female mice following early life and adult stress.Brain research · 2016Article
- Protease-activated receptors (PARs)--biology and role in cancer invasion and metastasis.Cancer metastasis reviews · 2015Review
- Neutrophil Elastase Activates Protease-activated Receptor-2 (PAR2) and Transient Receptor Potential Vanilloid 4 (TRPV4) to Cause Inflammation and Pain.The Journal of biological chemistry · 2015Article
- Review
- Protease-activated receptors in the Achilles tendon-a potential explanation for the excessive pain signalling in tendinopathy.Molecular pain · 2015Article
- New insights into protease-activated receptor 4 signaling pathways in the pathogenesis of inflammation and neuropathic pain: a literature review.Channels (Austin, Tex.) · 2015Review
- Proteinase activated-receptors-associated signaling in the control of gastric cancer.World journal of gastroenterology · 2014Review
- Diversification and specialization of touch receptors in skin.Cold Spring Harbor perspectives in medicine · 2014Review
- Protease-activated receptors as therapeutic targets in visceral pain.Current neuropharmacology · 2013Article
- Proteinase-activated receptors (PARs) - focus on receptor-receptor-interactions and their physiological and pathophysiological impact.Cell communication and signaling : CCS · 2013Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Thrombin, generated in the circulation during injury, cleaves proteinase-activated receptor 1 (PAR1) to stimulate plasma extravasation and granulocyte infiltration. However, the mechanism of thrombin-induced inflammation in intact tissues is unknown. We hypothesized that thrombin cleaves PAR1 on sensory nerves to release substance P (SP), which interacts with the neurokinin 1 receptor (NK1R) on endothelial cells to cause plasma extravasation. PAR1 was detected in small diameter neurons known to contain SP in rat dorsal root ganglia by immunohistochemistry and in situ hybridization. Thrombin and the PAR1 agonist TFLLR-NH(2) (TF-NH(2)) increased [Ca(2+)](i) >50% of cultured neurons (EC(50)s 24 mu ml(-1) and 1.9 microM, respectively), assessed using Fura-2 AM. The PAR1 agonist completely desensitized responses to thrombin, indicating that thrombin stimulates neurons through PAR1. Injection of TF-NH(2) into the rat paw stimulated a marked and sustained oedema. An NK1R antagonist and ablation of sensory nerves with capsaicin inhibited oedema by 44% at 1 h and completely by 5 h. In wild-type but not PAR1(-/-) mice, TF-NH(2) stimulated Evans blue extravasation in the bladder, oesophagus, stomach, intestine and pancreas by 2 - 8 fold. Extravasation in the bladder, oesophagus and stomach was abolished by an NK1R antagonist. Thus, thrombin cleaves PAR1 on primary spinal afferent neurons to release SP, which activates the NK1R on endothelial cells to stimulate gap formation, extravasation of plasma proteins, and oedema. In intact tissues, neurogenic mechanisms are predominantly responsible for PAR1-induced oedema.
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Registered trials
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