Toluene diisocyanate increases airway responsiveness to substance P and decreases airway neutral endopeptidase.
Toluene diisocyanate increases airway responsiveness to substance P and decreases airway neutral endopeptidase.
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甲苯二异氰酸酯增加气道对 P 物质的反应性并降低气道中性内肽酶。
DOI：
10.1172/jci113424
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
Borson,DB
中科院分区：
文献类型：
--
作者：
Sheppard,D;Thompson,JE;Scypinski,L;Dusser,D;Nadel,JA;Borson,DB
P物质及相关速激肽参与甲苯二异氰酸酯(TDI)引起的豚鼠气道高反应性。中性内肽酶(NEP)是P物质诱导反应的重要调节因子。为了验证暴露于TDI会通过抑制这种酶的活性来增加对P物质的反应性这一假设，我们确定了在给予药物抑制剂磷酰胺之前和之后，所研究的豚鼠在暴露于空气1h或3ppm TDI后1h所需的P物质剂量，以使肺阻力增加200%(PD200)。TDI暴露显著增加了对P物质的反应性。然而，在暴露于空气的动物中，亚磷酰胺引起的P物质剂量-反应曲线的左移明显大于暴露于TDI的动物，因此，暴露于空气或TDI的动物的PD200平均值在亚磷酰胺作用后并无差别。暴露于TDI后，气管NEP活性明显低于暴露于空气后，而两组的食道活动相同。这些结果表明，TDI暴露增加了豚鼠对P物质的支气管收缩反应，这在很大程度上是通过抑制呼吸道NEP实现的。
Substance P and related tachykinins contribute to the airway hyperresponsiveness caused by toluene diisocyanate (TDI) in guinea pigs. Neutral endopeptidase (NEP) is an important modulator of substance P-induced responses. To test the hypothesis that exposure to TDI would increase responsiveness to substance P by inhibiting activity of this enzyme, we determined the dose of substance P required to increase pulmonary resistance by 200% above baseline (PD200) before and after administration of the pharmacologic inhibitor phosphoramidon in guinea pigs studied 1 h after a 1-h exposure to air or 3 ppm TDI. TDI exposure increased responsiveness to substance P significantly. However, phosphoramidon caused a significantly greater leftward shift of the substance P dose-response curve in air-exposed animals than it did in TDI-exposed animals, so that after phosphoramidon, mean values of PD200 in animals exposed to air or TDI did not differ. Tracheal NEP activity was significantly less after exposure to TDI than after exposure to air, whereas activity in the esophagus was the same in both groups. These results suggest that TDI exposure increases the bronchoconstrictor responsiveness of guinea pigs to substance P, in large part through inhibition of airway NEP.
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影响因子：
4.7
作者：
C. Llorens;Bernard Malfroy;J. Schwartz;G. Gacel;B. Roques;J. Roy;Morgat Jl;F. Javoy‐Agid;Yves Agid
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Yves Agid
DOI：
10.1073/pnas.80.4.1120
发表时间：
1983-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
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作者：
LUNDBERG, JM;SARIA, A;FOLKERS, K
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影响因子：
1.7
作者：
Borson,DB;Corrales,R;Varsano,S;Gold,M;Viro,N;Caughey,G;Ramachandran,J;Nadel,JA
通讯作者：
Nadel,JA
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DOI：
10.1164/arrd.1983.127.6.686
发表时间：
1983
期刊：
The American review of respiratory disease
影响因子：
--
作者：
Holtzman,MJ;Fabbri,LM;O'Byrne,PM;Gold,BD;Aizawa,H;Walters,EH;Alpert,SE;Nadel,JA
通讯作者：
Nadel,JA
DOI：
10.1016/0091-6749(82)90202-0
发表时间：
1982
期刊：
The Journal of allergy and clinical immunology
影响因子：
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作者：
Brooks,SM
通讯作者：
Brooks,SM