Modulation of the bronchomotor effects of chemical mediators by prostaglandin F2 alpha in asthmatic subjects.
Modulation of the bronchomotor effects of chemical mediators by prostaglandin F2 alpha in asthmatic subjects.
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哮喘受试者中前列腺素 F2 α 对化学介质的支气管运动作用的调节。
DOI：
10.1164/arrd.1984.130.4.571
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发表时间：
1984
期刊：
影响因子：
--
通讯作者：
Norman,PS
中科院分区：
文献类型：
--
作者：
Fish,JE;Jameson,LS;Albright,A;Norman,PS
前列腺素F2α（PGF 2 α）是由人肺组织对多种刺激产生的，被广泛认为是支气管收缩介质。我们已经证明，浓度在1至100 μg/ml之间的PGF 2 α雾化吸入可引起剂量相关的支气管收缩，但在较高浓度下持续刺激可导致肺功能部分恢复至对照水平，这表明气道对进一步刺激不敏感。为探讨前列腺素F2 α（PGF 2 α）诱导气道不应性的机制和特异性，我们检测了PGF 2 α重复刺激、组胺重复刺激和PGF 2 α刺激后组胺诱发的支气管反应。在7名过敏性哮喘受试者中进行了3天的研究。对于每名受试者，每种激动剂的气雾剂浓度在整个研究期间保持恒定。以FEV 1随时间的变化百分比来测量反应，并在每个研究日的第一次和第二次激动剂激发之间进行比较。我们发现，预先用PGF 2 α刺激导致气道反应性降低，不仅对PGF 2 α，而且对组胺也是如此。相反，重复组胺刺激不能诱导类似的不应性，表明PGF 2 α诱导的反应性降低不是支气管收缩本身的非特异性效应。此外，PGF 2 α导致对组胺的反应降低的发现表明，气道反应性降低不是由于特异性PGF 2 α受体的下调。我们的研究结果表明，除了其支气管收缩特性，PGF 2 α可能在急性气道反应的调制中发挥作用。
Prostaglandin F2α(PGF2α) is generated by human lung tissue in response to a number off stimuli and is widely viewed as a bronchoconstrictor mediator. We have shown that aerosolized PGF2αin concentrations between 1 and 100 μg/ml caused dose-related bronchoconstriction, but that continued stimulation at higher concentrations resulted in a partial return of pulmonary function toward control, suggesting that airways were refractory to further stimulation. To explore the mechanism and specificity of airway refractoriness induced by PGF2α, we examined bronchomotor responses evoked by repeated PGF2αstimulation, repeated histamine stimulation, and PGF2αstimulation followed by histamine. Studies were carried out on 3 separate days in 7 subjects with allergic asthma. For each subject the aerosol concentration of each agonist remained constant throughout the study. Responses were measured as the percent change in FEV1versus time, and comparisons were made between the first and second agonist challenge of each study day. We found that prior stimulation with PGF2αresulted in diminished airway responsiveness, not only to PGF2αbut to histamine as well. In contrast, similar refractoriness could not be induced by repeated histamine stimulation, indicating that the PGF2α-induced decrease in responsiveness was not a nonspecific effect of bronchoconstriction per se. Further, the finding that PGF2αcaused a decrease in the response to histamine suggests that diminished airway responsiveness was not due to down-regulation of specific PGF2αreceptors. Our findings suggest that in addition to its bronchoconstrictor properties, PGF2αmay play a role in the modulation of acute airway responses.