Prostaglandin involvement in lung C-fiber activation by substance P in guinea pigs.
J Appl Physiol (1985)
; 100(6): 1918-27, 2006 Jun.
Article
de En
| MEDLINE
| ID: mdl-16455813
ABSTRACT
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 F2alpha. Therefore, exogenously applied SP stimulates an indomethacin-sensitive pathway leading to C-fiber activation.
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Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Substance P
/
Prostaglandines
/
Neurofibres non-myélinisées
/
Poumon
Limites:
Animals
Langue:
En
Journal:
J Appl Physiol (1985)
Sujet du journal:
FISIOLOGIA
Année:
2006
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique