Aerosolized neutral endopeptidase reverses ozone-induced airway hyperreactivity to substance P
- Department of Medicine, Rush University, Chicago, IL (United States)
The authors 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 nmol.min-1.mg protein-1 for the ozone-exposed group and 25.1 +/- 2.4 nmol.min-1.mg 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)
- OSTI ID:
- 5266708
- Journal Information:
- Journal of Applied Physiology (1985); (United States), Vol. 72:3; ISSN 8750-7587
- Country of Publication:
- United States
- Language:
- English
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KININS
BIOCHEMICAL REACTION KINETICS
OZONE
BIOLOGICAL EFFECTS
PEPTIDE HYDROLASES
ENZYME ACTIVITY
RESPIRATORY SYSTEM
SENSITIVITY
AEROSOLS
CELL MEMBRANES
DOSE-RESPONSE RELATIONSHIPS
GUINEA PIGS
LIQUID COLUMN CHROMATOGRAPHY
METABOLISM
ANIMALS
CELL CONSTITUENTS
CHROMATOGRAPHY
COLLOIDS
DISPERSIONS
ENZYMES
HYDROLASES
KINETICS
MAMMALS
MEMBRANES
ORGANIC COMPOUNDS
PEPTIDES
POLYPEPTIDES
PROTEINS
REACTION KINETICS
RODENTS
SEPARATION PROCESSES
SOLS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology