ArticleThe Journal of physiology2003
Mast cell tryptase and proteinase-activated receptor 2 induce hyperexcitability of guinea-pig submucosal neurons.
Article in The Journal of physiology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
What it found
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Who cites it
78 citing papers in PubMed, 183 citations in OpenAlex.
- Mast Cells in Neuroimmune Interactions: Mechanisms, Pathophysiological Roles, and Therapeutic Implications.Molecular neurobiology · 2026Review
- The Mast Cell-Substance P Neuroimmune Axis in Allergic Contact Dermatitis and Atopic Dermatitis: Molecular Mechanisms and Pathophysiological Perspectives.Current issues in molecular biology · 2026Review
- The SP-MrgprX2 Axis in Allergic Rhinitis: a Neuro-immune Paradigm Beyond IgE-mediated Inflammation.Clinical reviews in allergy & immunology · 2026Review
- Article
- The Mast Cell-PAR2-TRP Axis: A Convergent Mechanism for Visceral Hypersensitivity Independent of Divergent Motility in IBS.Biomolecules · 2026Review
- Protease-activated receptors act as a liaison between metabolism and inflammation.Inflammopharmacology · 2026Review
- The Interplay Between Immunological Status and Gut Microbial Dysbiosis in the Development of the Symptoms of Irritable Bowel Syndrome: A Systematic Review with Meta-Analysis.Digestive diseases and sciences · 2026Review
- Ganhai Weikang Capsules ameliorate functional dyspepsia in rats by modulating gut microbiota and host metabolic homeostasis.Frontiers in pharmacology · 2026Article
- Enteric nervous system in microbiota-associated gut inflammation.Frontiers in immunology · 2026Review
- Purinergic signaling in the gut neuro-glial-immune axis: mechanisms of homeostasis, inflammation, and gastrointestinal dysfunction.Frontiers in gastroenterology (Lausanne, Switzerland) · 2026Review
- Protease-Activated Receptors (PARs): Biology and Therapeutic Potential in Perioperative Stroke.Translational stroke research · 2025Review
- Efficacy of MEDI0618, a pH-dependent monoclonal antibody targeting PAR2, in preclinical models of migraine.Brain : a journal of neurology · 2025Article
- Comparisons of different electrical stimulation modalities for treating visceral pain in a rodent model of irritable bowel syndrome.Bioelectronic medicine · 2024Article
- TLR-4: a promising target for chemotherapy-induced peripheral neuropathy.Molecular biology reports · 2024Review
- Non-invasive neuromodulation: an emerging intervention for visceral pain in gastrointestinal disorders.Bioelectronic medicine · 2023Review
- The enteric nervous system.Physiological reviews · 2023Review
- Immune sensing of food allergens promotes aversive behaviour.bioRxiv : the preprint server for biology · 2023Article
- Neuroimmune regulation in Hirschsprung's disease associated enterocolitis.Frontiers in immunology · 2023Review
- Protease-activated receptors in health and disease.Physiological reviews · 2023Review
- Altered functional responses by PAR1 agonist in murine dextran sodium sulphate-treated colon.Scientific reports · 2022Article
18 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Mast cells that are in close proximity to autonomic and enteric nerves release several mediators that cause neuronal hyperexcitability. This study examined whether mast cell tryptase evokes acute and long-term hyperexcitability in submucosal neurons from the guinea-pig ileum by activating proteinase-activated receptor 2 (PAR2) on these neurons. We detected the expression of PAR2 in the submucosal plexus using RT-PCR. Most submucosal neurons displayed PAR2 immunoreactivity, including those colocalizing VIP. Brief (minutes) application of selective PAR2 agonists, including trypsin, the activating peptide SL-NH2 and mast cell tryptase, evoked depolarizations of the submucosal neurons, as measured with intracellular recording techniques. The membrane potential returned to resting values following washout of agonists, but most neurons were hyperexcitable for the duration of recordings (> 30 min-hours) and exhibited an increased input resistance and amplitude of fast EPSPs. Trypsin, in the presence of soybean trypsin inhibitor, and the reverse sequence of the activating peptide (LR-NH2) had no effect on neuronal membrane potential or long-term excitability. Degranulation of mast cells in the presence of antagonists of established excitatory mast cell mediators (histamine, 5-HT, prostaglandins) also caused depolarization, and following washout of antigen, long-term excitation was observed. Mast cell degranulation resulted in the release of proteases, which desensitized neurons to other agonists of PAR2. Our results suggest that proteases from degranulated mast cells cleave PAR2 on submucosal neurons to cause acute and long-term hyperexcitability. This signalling pathway between immune cells and neurons is a previously unrecognized mechanism that could contribute to chronic alterations in visceral function.
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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.