Co‐axial bioassay of a smooth muscle relaxant factor released from guinea‐pig tracheal epithelium
Co‐axial bioassay of a smooth muscle relaxant factor released from guinea‐pig tracheal epithelium
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豚鼠气管上皮释放的平滑肌松弛因子的同轴生物测定
DOI：
10.1111/j.1476-5381.1989.tb11791.x
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发表时间：
1989
影响因子：
7.3
通讯作者：
R. Goldie
中科院分区：
文献类型：
--
作者：
L. Fernandes;J. Paterson;R. Goldie
1 在同轴生物测定系统中评估了豚鼠气管释放上皮源性松弛因子 (EpDRF) 的能力。 2 组胺 (100 μm) 和醋甲胆碱 (25 μm) 可能通过释放内皮衍生松弛因子 (EDRF) 引起大鼠离体主动脉的内皮依赖性松弛。相比之下，内皮剥脱的大鼠主动脉并没有对这些药物做出反应而松弛。 3 在同轴生物测定系统中检测到乙酰甲胆碱的 EDRF 释放，该系统由完整的兔主动脉管（EDRF 供体）和去内皮的大鼠主动脉条（测定制剂）组成。这些结果表明 EDRF 从供体转移到测定制剂中，从而验证了同轴生物测定方法。 4 在同轴组件中用上皮完整的豚鼠气管导管组织替代内皮完整的兔主动脉管，仍然允许检测制剂对组胺或醋甲胆碱产生松弛反应。从系统中取出完整的气管导管，或从同轴制剂中的供体气管导管上去除上皮，消除了这种松弛反应。这些观察结果与组胺或乙酰甲胆碱诱导的气管释放上皮源性松弛因子（EpDRF）一致。 5 在由完整豚鼠气管和去内皮的大鼠主动脉组成的同轴组件中，组胺和醋甲胆碱产生浓度依赖性、EpDRF 诱导的主动脉舒张。产生 50% 最大松弛 (EC50) 的组胺和乙酰甲胆碱的平均浓度分别为 39.8 μm 和 2.7 μm。美吡拉敏 (2 μm) 的存在会抑制组胺诱导的松弛，阿托品 (0.1 μm) 会抑制乙酰甲胆碱的反应。 6 亚甲基蓝 (50 μm) 对此类松弛反应没有影响，表明 EpDRF 不会激活鸟苷酸环化酶。此外，环加氧酶抑制剂吲哚美辛 (5 μm)、环加氧酶/脂氧合酶抑制剂 BW 755C (150 μm) 和白三烯受体拮抗剂 FPL 55712 (10 μm) 均未能显着改变 EpDRF 介导的血管平滑肌松弛，表明 EpDRF 不是前列腺素类药物。血小板激活因子（Paf）未能引起内皮剥脱的大鼠主动脉舒张，表明该介质也不是 EpDRF。 7 EpDRF 也从人类支气管段释放。 8 这项研究为非患病气道组织释放 EpDRF 提供了直接证据，并进一步表明健康气道对痉挛原的反应性是通过内源性保护性解痉物质的释放来调节的。哮喘的支气管高反应性可能部分是由这种抑制信号的产生减弱引起的。
1 The ability of guinea‐pig trachea to release an epithelium‐derived relaxant factor (EpDRF) was assessed in a co‐axial bioassay system. 2 Histamine (100 μm) and methacholine (25 μm) caused endothelium‐dependent relaxation of rat isolated aorta, presumably via the release of endothelium‐derived relaxant factor (EDRF). In contrast, endothelium‐denuded rat aorta did not relax in response to these agents. 3 EDRF release was detected in response to methacholine in a co‐axial bioassay system, consisting of intact rabbit aorta tube (EDRF donor) and endothelium‐denuded rat aorta strip (assay preparation). These results indicated the transfer of EDRF from a donor to an assay preparation, thereby validating the co‐axial bioassay method. 4 Substitution of endothelium‐intact rabbit aorta tube by epithelium‐intact guinea‐pig tracheal tube tissue in co‐axial assemblies, still allowed the assay preparation to relax in response to histamine or methacholine. Removal of the intact tracheal tube from the system, or removal of the epithelium from the donor tracheal tube in co‐axial preparations, abolished such relaxant responses. These observations are consistent with histamine‐ or methacholine‐induced release of an epithelium‐derived relaxant factor (EpDRF) from the trachea. 5 In the co‐axial assembly comprising intact guinea‐pig trachea and endothelium‐denuded rat aorta, histamine and methacholine produced concentration‐dependent, EpDRF‐induced aortic relaxation. Mean concentrations of histamine and methacholine producing 50% of the maximum relaxation (EC50) were 39.8 μm and 2.7 μm respectively. Histamine‐induced relaxation was inhibited in the presence of mepyramine (2 μm) and responses to methacholine were inhibited by atropine (0.1 μm). 6 Methylene blue (50 μm) had no effect on such relaxant responses, indicating that EpDRF does not activate guanylate cyclase. Furthermore, the cyclo‐oxygenase inhibitor indomethacin (5 μm), the cyclo‐oxygenase/lipoxygenase inhibitor BW 755C (150 μm) and the leukotriene receptor antagonist FPL 55712 (10 μm) each failed significantly to alter EpDRF‐mediated relaxation of vascular smooth muscle suggesting that EpDRF is not a prostanoid. Platelet activating factor (Paf) failed to cause relaxation of endothelium‐denuded rat aorta, indicating that this mediator was also not EpDRF. 7 EpDRF was also released from human bronchial segments. 8 This study provides direct evidence for the release of an EpDRF from non‐diseased airway tissue and further suggests that healthy airway reactivity to spasmogens is modulated by the release of an endogenous protective, spasmolytic substance. The bronchial hyperreactivity of asthma may be partly caused by attenuated production of such an inhibitory signal.
DOI：
--
发表时间：
1985-03
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
W. Martin;G. Villani;D. Jothianandan;R. Furchgott
通讯作者：
W. Martin;G. Villani;D. Jothianandan;R. Furchgott
呼吸道上皮抑制支气管平滑肌张力。
DOI：
10.1152/jappl.1985.58.3.834
发表时间：
1985
期刊：
Journal of applied physiology (Bethesda, Md. : 1985)
影响因子：
--
作者：
Flavahan,NA;Aarhus,LL;Rimele,TJ;Vanhoutte,PM
通讯作者：
Vanhoutte,PM
粘膜去除对豚鼠气道平滑肌反应性的影响。
DOI：
10.1042/cs0700571
发表时间：
1986
期刊：
Clinical science (London, England : 1979)
影响因子：
--
作者：
Murlas,C
通讯作者：
Murlas,C