Differences in the distribution and characteristics of tachykinin NK1 binding sites between human and guinea pig lung
Differences in the distribution and characteristics of tachykinin NK1 binding sites between human and guinea pig lung
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人和豚鼠肺速激肽NK1结合位点分布及特征的差异
DOI：
10.1111/j.1476-5381.1994.tb17154.x
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发表时间：
1994
影响因子：
7.3
通讯作者：
J. Polak
中科院分区：
文献类型：
--
作者：
D. A. Walsh;M. Salmon;R. Featherstone;J. Wharton;M. Church;J. Polak
1采用[125I]-Bolton Hunter标记的P物质([125I]-BH-SP)体外受体放射自显影技术，比较了速激肽NK1结合位点在人和豚鼠肺中的分布和特征。此外，还在豚鼠肺中测定了卵清蛋白致敏和激发对上述部位的影响。2[125I]-BH-SP与人和豚鼠肺微血管内皮细胞特异性结合，与微血管内皮细胞高亲和力结合，但仅与豚鼠肺的支气管平滑肌和肺动脉中膜结合。3豚鼠支气管平滑肌与[125I]-BH-SP的特异性结合在15 0~80 0μm范围内与气道内径呈正相关，气管的结合密度低于主支气管。4速激肽可抑制[125I]-BH-SP的结合，其亲和力顺序为：人微血管SP>；NKA>；NKB和豚鼠支气管和肺动脉。Nka在人微血管中对BH-SP结合部位的亲和力高于在豚鼠组织中(P<；0.0001)，表明人和豚鼠NK1受体对速激肽的选择性不同。5在人和豚鼠肺中，速激肽受体特异性拮抗剂FK888(NK1选择性拮抗剂)和FK224(NK1/NK2混合拮抗剂)均可抑制[125I]-BH-SP结合，FK888与SP的亲和力相当，FK224的亲和力比FK224高500倍。在豚鼠动脉和支气管内，SP、NKA、NKB和FK888对[125I]-BH-SP结合部位的亲和力相似。6[125I]-BH-SP结合位点在卵蛋白致敏和激发的豚鼠肺和幼年动物中的分布、密度和特征相似。7用[125I]-BH-SP标记的NK1结合位点在豚鼠和人肺中的分布和特征的差异表明，用豚鼠模型研究速激肽在肺部疾病中的作用是有局限性的。然而，NKJ结合部位在人和豚鼠肺内的微血管分布相似，提示选择性速激素受体拮抗剂FK888和FK224可能在人的呼吸道炎症治疗中有用。
1 The distribution and characteristics of tachykinin NK1 binding sites have been compared in human and guinea pig lung using quantitative in vitro receptor autoradiography with [125I]‐Bolton Hunter‐labelled substance P ([125I]‐BH‐SP). In addition, the effects on these sites of ovalbumin sensitization and challenge have been determined in guinea pig lung. 2 [125I]‐BH‐SP bound specifically and with high affinity to microvascular endothelium in both human and guinea pig lung, but to bronchial smooth muscle and pulmonary artery media in only guinea pig lung. 3 Specific binding of [125I]‐BH‐SP to guinea pig bronchial smooth muscle was positively correlated with airway diameter in the range 150–800 μm and was less dense in trachea than in main bronchi. 4 [125I]‐BH‐SP binding was inhibited by tachykinins with rank orders of affinity of SP > NKA > NKB (human microvessels) and SP > NKA = NKB (guinea pig bronchi and pulmonary arteries). NKA displayed a higher affinity for [125]‐BH‐SP binding sites in human microvessels than in guinea pig tissues (P < 0.0001), indicating differences in selectivity for tachykinins between human and guinea pig NK1 receptors. 5 In both human and guinea pig lung, [125I]‐BH‐SP binding was inhibited by the specific tachykinin receptor antagonists FK888 (NK1 selective antagonist) and FK224 (mixed NK1/NK2 antagonist), with FK888 displaying equal affinity to SP and > 500 times higher affinity than FK224. SP, NKA, NKB and FK888 exhibited similar affinities for [125I]‐BH‐SP binding sites in both guinea pig arteries and bronchi. 6 Similar distributions, densities and characteristics of [125I]‐BH‐SP binding sites were demonstrated in ovalbumin‐sensitized and ‐challenged guinea‐pig lung and in naive animals. 7 Differences in the distribution and characteristics of NK1 binding sites labelled with [125I]‐BH‐SP between guinea pig and human lung suggest limitations in the use of guinea pig models for studying roles of tachykinins in pulmonary disease. However, the similar microvascular distributions of NKj binding sites in human and guinea pig lung suggest that the selective tachykinin receptor antagonists FK888 and FK224 may be useful in the management of airway inflammation in man.
惊厥巴比妥类药物对内源性乙酰胆碱释放和钠依赖性高亲和力胆碱摄取的影响。
DOI：
--
发表时间：
1983
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
HoltmanJr,JR;Richter,JA
通讯作者：
Richter,JA
神经源性炎症在豚鼠气管抗原诱导血管外渗中的作用。
DOI：
--
发表时间：
1993
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Bertrand,C;Geppetti,P;Baker,J;Yamawaki,I;Nadel,JA
通讯作者：
Nadel,JA