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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Aerosolized neutral endopeptidase reverses ozone-induced airway hyperreactivity to substance P.

We investigated the effects of ozone exposure (3.0 ppm, 2 h) on airway neutral endopeptidase ( NEP) activity and bronchial reactivity to substance P in guinea pigs. Reactivity after ozone or air exposure was determined by measuring specific airway resistance in intact unanesthetized spontaneously breathing animals in response to increasing doses of intravenous substance P boluses. The effective dose of substance P (in micrograms) that produced a doubling of baseline specific airway resistance (ED200SP) was determined by interpolation of cumulative substance P dose-response curves. NEP activity was measured in tracheal homogenates made from each animal of other groups exposed to either ozone or room air. By reverse-phase high-pressure liquid chromatography, this activity was characterized by the phosphoramidon-inhibitable cleavage of alanine-p-nitroaniline from succinyl-(Ala)3-p-nitroaniline in the presence of 100 microM amastatin. Mean values of the changes in log ED200SP were 0.27 +/- 0.07 (SE) for the ozone-exposed group and 0.08 +/- 0.04 for the air-exposed group. We found that phosphoramidon significantly increased substance P reactivity in the air-exposed animals (P less than 0.01), but it had no effect in the ozone-exposed group. This finding was associated with a significant reduction in tracheal homogenate NEP activity of ozone-exposed animals compared with controls: mean values were 18.1 +/- 1.9 protein-1 for the ozone-exposed group and 25.1 +/- 2.4 protein-1 for air-exposed animals (P less than 0.05). Inhalation of an aerosolized NEP preparation, partially purified from guinea pig kidney, reversed the substance P hyperreactivity produced by ozone exposure.(ABSTRACT TRUNCATED AT 250 WORDS)[1]


  1. Aerosolized neutral endopeptidase reverses ozone-induced airway hyperreactivity to substance P. Murlas, C.G., Lang, Z., Williams, G.J., Chodimella, V. J. Appl. Physiol. (1992) [Pubmed]
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