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This Article Full Text Free Full Text (PDF) Free All Versions of this Article: 100/6/1918    most recent 01276.2005v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Bergren, D. R. Search for Related Content PubMed PubMed Citation Articles by Bergren, D. R.

Prostaglandin involvement in lung C-fiber activation by substance P in guinea pigs

Department of Biomedical Sciences, School of Medicine, Creighton University, Omaha, Nebraska

Submitted 4 October 2005 ; accepted in final form 25 January 2006

Airway hyperresponsiveness is a cardinal feature of asthma. Lung C-fiber activation induces central and local defense reflexes that may contribute to airway hyperresponsiveness. Initial studies show that substance P (SP) activates C fibers even though it is produced and released by these same C fibers. SP may induce release of other endogenous mediators. Bradykinin (BK) is an endogenous mediator that activates C fibers. The hypothesis was tested that SP activates C fibers via BK release. Guinea pigs were anesthetized, and C-fiber activity (FA), pulmonary insufflation pressure (PIP), heart rate, and arterial blood pressure were monitored before and after intravenous injection of capsaicin (Cap), SP, and BK. Identical agonist challenges were repeated after infusion of an antagonist cocktail of des-Arg⁹-[Leu⁸]-BK (10^–3 M, B₁ antagonist), and HOE-140 (10^–4 M, B₂ antagonist). After antagonist administration, BK increased neither PIP nor FA. Increases in neither PIP nor FA were attenuated after Cap or SP challenge. In a second series of experiments, Cap and SP were injected before and after infusion of indomethacin (1 mg/kg iv) to determine whether either agent activates C fibers through release of arachidonic acid metabolites. Indomethacin administration decreased the effect of SP challenge on FA but not PIP. The effect of Cap on FA or PIP was not altered by indomethacin. In subsequent experiments, C fibers were activated by prostaglandin E₂ and F₂. Therefore, exogenously applied SP stimulates an indomethacin-sensitive pathway leading to C-fiber activation.

C-fiber activity