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Tachykinins contribute to the acute airways response to allergen in sheep actively sensitized to Ascaris suum
Author(s) -
REYNOLDS Paul N,
RICE Anthony J,
REYNOLDS Ann M,
THORNTON Andrew T,
HOLMES Mark D,
SCICCHITANO Raffaele
Publication year - 1997
Publication title -
respirology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 85
eISSN - 1440-1843
pISSN - 1323-7799
DOI - 10.1111/j.1440-1843.1997.tb00078.x
Subject(s) - ascaris suum , phosphoramidon , medicine , ascaris , capsaicin , desensitization (medicine) , fenoterol , allergen , immunology , substance p , asthma , allergy , pharmacology , receptor , neuropeptide , helminths , endothelin receptor
Tachykinins, found in sensory nerves, have effects in the airways which suggest that they may contribute to the pathogenesis of asthma. We aimed to find evidence for tachykinin involvement in the immediate airway response to allergen in a sheep model of experimental asthma. Twenty‐four sheep were actively sensitized to Ascaris suum , then challenged with nebulized Ascaris extract in a dose‐response fashion. Change in lung resistance (R L ) in response to challenge was measured. Responder sheep (those with an increase in R L of >100% over baseline) that had reproducible responses over three challenges were identified ( n = 4 sheep) and a PC 100 (number of breaths of extract required to induce a 100% increase in R L ) was determined. The effect of the neutral endopeptidase inhibitor phosphoramidon, the NK‐1 receptor‐specific antagonist CP 96, 345 and capsaicin desensitization on the R L response to Ascaris challenge was then assessed. Administration of phosphoramidon before Ascaris decreased the PC 100 to 31 ± 7% of the PC 100 seen with Ascaris alone ( P <0.05), whereas CP 96,345 and capsaicin desensitization increased the PC 100 to 285 ± 41% and 555 ± 93% respectively ( P <0.05 for both). These findings suggest that endogenous tachykinins are released in response to allergen challenge and that they contribute to the immediate increase in R L .