| Protease-activated receptor-2 activation exaggerates TRPV1-mediated cough in guinea pigs. | |
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MedLine Citation:
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PMID: 16627674 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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A lowered threshold to the cough response frequently accompanies chronic airway inflammatory conditions. However, the mechanism(s) that from chronic inflammation results in a lowered cough threshold is poorly understood. Irritant agents, including capsaicin, resiniferatoxin, and citric acid, elicit cough in humans and in experimental animals through the activation of the transient receptor potential vanilloid 1 (TRPV1). Protease-activated receptor-2 (PAR2) activation plays a role in inflammation and sensitizes TRPV1 in cultured sensory neurons by a PKC-dependent pathway. Here, we have investigated whether PAR2 activation exaggerates TRPV1-dependent cough in guinea pigs and whether protein kinases are involved in the PAR2-induced cough modulation. Aerosolized PAR2 agonists (PAR2-activating peptide and trypsin) did not produce any cough per se. However, they potentiated citric acid- and resiniferatoxin-induced cough, an effect that was completely prevented by the TRPV1 receptor antagonist capsazepine. In contrast, cough induced by hypertonic saline, a stimulus that provokes cough in a TRPV1-independent manner, was not modified by aerosolized PAR2 agonists. The PKC inhibitor GF-109203X, the PKA inhibitor H-89, and the cyclooxygenase inhibitor indomethacin did not affect cough induced by TRPV1 agonists, but abated the exaggeration of this response produced by PAR2 agonists. In conclusion, PAR2 stimulation exaggerates TRPV1-dependent cough by activation of diverse mechanism(s), including PKC, PKA, and prostanoid release. PAR2 activation, by sensitizing TRPV1 in primary sensory neurons, may play a role in the exaggerated cough observed in certain airways inflammatory diseases such as asthma and chronic obstructive pulmonary disease. |
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Authors:
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Raffaele Gatti; Eunice Andre; Silvia Amadesi; Thai Q Dinh; Axel Fischer; Nigel W Bunnett; Selena Harrison; Pierangelo Geppetti; Marcello Trevisani |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2006-04-20 |
Journal Detail:
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Title: Journal of applied physiology (Bethesda, Md. : 1985) Volume: 101 ISSN: 8750-7587 ISO Abbreviation: J. Appl. Physiol. Publication Date: 2006 Aug |
Date Detail:
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Created Date: 2006-07-19 Completed Date: 2006-09-12 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8502536 Medline TA: J Appl Physiol Country: United States |
Other Details:
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Languages: eng Pagination: 506-11 Citation Subset: IM |
Affiliation:
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Center of Excellence for the study of Inflammation, Dept. of Clinical & Experimental Medicine, Pharmacology Section, Univ. of Ferrara, 44100 Ferrara, Italy. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Capsaicin / analogs & derivatives, pharmacology Citric Acid / adverse effects Cough / chemically induced, physiopathology* Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors, physiology Cyclooxygenase Inhibitors / pharmacology Diterpenes / adverse effects Guinea Pigs / physiology* Indomethacin / pharmacology Inflammation Isoquinolines / pharmacology Male Neurons, Afferent / physiology Protein Kinase C / antagonists & inhibitors, physiology Protein Kinase Inhibitors / pharmacology Receptor, PAR-2 / physiology* Saline Solution, Hypertonic / adverse effects Sulfonamides / pharmacology TRPV Cation Channels / physiology* Trypsin / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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DK-43207/DK/NIDDK NIH HHS; DK-57480/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cyclooxygenase Inhibitors; 0/Diterpenes; 0/Isoquinolines; 0/Protein Kinase Inhibitors; 0/Receptor, PAR-2; 0/Saline Solution, Hypertonic; 0/Sulfonamides; 0/TRPV Cation Channels; 0/capsazepine; 127243-85-0/H 89; 404-86-4/Capsaicin; 53-86-1/Indomethacin; 57444-62-9/resiniferatoxin; 77-92-9/Citric Acid; EC 2.7.11.11/Cyclic AMP-Dependent Protein Kinases; EC 2.7.11.13/Protein Kinase C; EC 3.4.21.4/Trypsin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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