Aerosolized neutral endopeptidase reverses ozone-induced airway hyperreactivity to substance P.
Aerosolized neutral endopeptidase reverses ozone-induced airway hyperreactivity to substance P.
复制标题
雾化中性肽链内切酶可逆转臭氧引起的气道对 P 物质的高反应性。
DOI：
10.1152/jappl.1992.72.3.1133
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
Chodimella,V
中科院分区：
文献类型：
--
作者：
Murlas,CG;Lang,Z;Williams,GJ;Chodimella,V
我们研究了臭氧暴露（3.0 ppm，2小时）对豚鼠气道中性内肽酶（NEP）活性和支气管对P物质的反应性的影响。臭氧或空气暴露后的反应性通过测量完整的未麻醉的自主呼吸动物对增加剂量的静脉内P物质推注的响应的比气道阻力来确定。P物质的有效剂量（微克），产生了基线比气道阻力（ED 200 SP）的两倍，通过插值的累积P物质的剂量-反应曲线。在从暴露于臭氧或室内空气的其他组的每只动物制备的气管匀浆中测量NEP活性。通过反相高压液相色谱法，该活性的特征在于在100 μ M amastatin存在下丙氨酸-对硝基苯胺从琥珀酰-（Ala）3-对硝基苯胺的磷酰胺可降解裂解。暴露于臭氧组和暴露于空气组的log ED 200 SP变化的平均值分别为0.27 +/- 0.07（SE）和0.08 +/- 0.04。我们发现，phosphoramidon显着增加P物质的反应性在空气暴露的动物（P <0.01），但它没有影响臭氧暴露组。与对照组相比，这一发现与臭氧暴露动物气管匀浆NEP活性的显著降低有关：臭氧暴露组的平均值为18.1 +/- 1.9 nmol.min-1.mg蛋白质-1，空气暴露组的平均值为25.1 +/- 2.4 nmol.min-1.mg蛋白质-1（P <0.05）。吸入雾化的NEP制剂，部分纯化豚鼠肾脏，逆转了臭氧暴露产生的P物质高反应性。（250字处删节）
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 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)