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Influence of influenza A infection on capsaicin-induced responses in murine airways

tetano

Editor, Senior Moderator
J Pharmacol Exp Ther. 2011 Nov 7. [Epub ahead of print]
Influence of influenza A infection on capsaicin-induced responses in murine airways.
Taylor SJ, Mann TS, Henry PJ.
Source

University of Western Australia.
Abstract

The principal aim of the study was to determine the influence of influenza A virus infection on capsaicin-induced relaxation responses in mouse isolated tracheal segments, and to clarify underlying mechanisms. Anaesthetised mice were intranasally inoculated with influenza A/PR-8/34 virus (VIRUS) or vehicle (SHAM), and four days later tracheal segments were harvested for isometric tension recording, biochemical and histologic analyses. Capsaicin induced dose-dependent relaxation responses in carbachol-contracted SHAM trachea (e.g. 10 ?M capsaicin produced 66?4% relaxation, n=11), which were significantly inhibited by capsazepine (TRPV1 antagonist), L-733,060 (NK1 receptor antagonist), indomethacin (COX inhibitor) and the combination of AH6809 and AH23848 (EP2 and EP4 receptor antagonists), indicating that capsaicin-induced relaxation involved the TRPV1-mediated release of SP, activation of epithelial NK1 receptors and production of COX products capable of activating relaxant EP2/EP4 receptors. Consistent with this postulate, capsaicin-induced relaxation was associated with significant release of SP and PGE2 from mouse tracheal segments. As expected, influenza A virus infection was associated with widespread disruption of the tracheal epithelium. Tracheal segments from VIRUS mice responded weakly to capsaicin (7?3% relaxation) and were 25-fold less responsive to SP than tracheas from SHAM mice. In contrast, relaxation responses to exogenous PGE2 and to the β-adrenoceptor agonist isoprenaline were not inhibited in VIRUS trachea. Virus infection was associated with impaired capsaicin-induced release of PGE2, but release of SP was not affected. In summary, influenza A virus infection profoundly inhibits capsaicin- and SP-induced relaxation responses, most likely by inhibiting the production of PGE2.

PMID:
22062353
[PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/pubmed/22062353
 
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