首页> 外文期刊>Life sciences >SR 142801, a tachykinin NK(3) receptor antagonist, prevents beta(2)-adrenoceptor agonist-induced hyperresponsiveness to neurokinin A in guinea-pig isolated trachea.
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SR 142801, a tachykinin NK(3) receptor antagonist, prevents beta(2)-adrenoceptor agonist-induced hyperresponsiveness to neurokinin A in guinea-pig isolated trachea.

机译:SR 142801,一种速激肽NK(3)受体拮抗剂,可防止β(2)-肾上腺素受体激动剂诱导的豚鼠离体气管对神经激肽A的过度反应。

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摘要

We investigated whether fenoterol was able to enhance contractile responsiveness to neurokinin A (NKA) on the guinea-pig isolated trachea. We then studied the effects of two inhibitors of nuclear factor kappa B (NFkappaB), gliotoxin and pyrrolidine dithiocarbamate, and of the tachykinin NK(1), NK(2) and NK(3) receptor antagonists, SR 140333, SR 48968 and SR 142801 and determined whether tachykinin receptor gene expression was up-regulated in the trachea after exposure to fenoterol. Fenoterol (0.1 microM, 15 h, 21 degrees C) induced an increased contractile response to NKA (mean of difference in maximal tension between control and fenoterol +/- S.E.M; +0.47 +/- 0.14 g, n = 26, P < 0.01). This hyperresponsiveness was strongly reduced by co-incubation with gliotoxin (0.1 microg/ml) or pyrrolidine dithiocarbamate (0.1 mM) and abolished by SR 140333 (0.1 microM) and SR 142801 (0.1 microM). SR 48968 (0.1 microM) diminished the tracheal contractility to NKA but failed to reduce the hyperreactivity induced by fenoterol. Tachykinin NK(1) receptor (NK(1)R), NK(2) receptor (NK(2)R) and NK(3) receptor (NK(3)R) gene expression was analyzed by semiquantitative RT-PCR. Compared to control tissues, NK(1)R and NK(2)R mRNA expression was increased by about 1.6-fold and 1.4-fold, respectively, in tissues treated with fenoterol. We were unable to detect the presence of NK(3)R mRNA in the guinea-pig trachea. In conclusion, fenoterol induces tracheal hyperresponsiveness to NKA and an up-regulation of NK(1)R and NK(2)R gene expression. The hyperresponsiveness implicates the NFkappaB pathway and is abolished by tachykinin NK(1) (SR 140333) and NK(3) (SR 142801) receptor antagonists.
机译:我们调查了非诺特罗是否能够增强豚鼠离体气管对神经激肽A(NKA)的收缩反应。然后,我们研究了两种核因子κB(NFkappaB)抑制剂,gliotoxin和吡咯烷二硫代氨基甲酸酯以及速激肽NK(1),NK(2)和NK(3)受体拮抗剂SR 140333,SR 48968和SR的作用142801,并确定暴露于非诺特罗后气管中速激肽受体基因的表达是否上调。非诺特罗(0.1 microM,15 h,21摄氏度)引起对NKA的收缩反应增加(对照组和非诺特罗+/- SEM之间最大张力差异的平均值; +0.47 +/- 0.14 g,n = 26,P <0.01 )。通过与葡聚糖毒素(0.1 microg / ml)或吡咯烷二硫代氨基甲酸酯(0.1 mM)共同孵育可大大降低这种高反应性,并由SR 140333(0.1 microM)和SR 142801(0.1 microM)消除。 SR 48968(0.1 microM)减少了对NKA的气管收缩性,但未能降低非诺特罗引起的反应过度。通过半定量RT-PCR分析了速激肽NK(1)受体(NK(1)R),NK(2)受体(NK(2)R)和NK(3)受体(NK(3)R)的基因表达。与对照组织相比,在用非诺特罗处理的组织中,NK(1)R和NK(2)R mRNA表达分别增加了约1.6倍和1.4倍。我们无法检测到豚鼠气管中NK(3)R mRNA的存在。最后,非诺特罗诱导气管对NKA的高反应性和NK(1)R和NK(2)R基因表达的上调。高反应性牵涉NFkappaB途径,并被速激肽NK(1)(SR 140333)和NK(3)(SR 142801)受体拮抗剂消除。

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