Wagner U, Fehmann H, Bredenbröker D, Klüber D, Lange A, Wichert P
Department of Internal Medicine, Philipps-University, Marburg/Lahn, Germany.
Neuropeptides. 1999 Feb;33(1):55-61. doi: 10.1054/npep.1999.0014.
Tachykinins like substance P (SP), neurokinin A (NKA), neurokinin B (NKB) differentially stimulate airway mucus secretion with the following rank order of potency in rat trachea: SP>NKA>NKB. These differential actions are most likely due to different affinities to the tachykinin receptors, termed neurokinin (NK)(1), NK(2)and NK(3). In this study we characterized the receptor subtype responsible for the differential secretagogue effects in rat trachea by means of selective receptor antagonists and receptor agonists.SR 140333 [NK(1)-antagonist] completely inhibited SP action (283,29+/-21, 12%-->84,53+/-4, 09%; P<0,01) and significantly reduced the effects of NKA (179,08+/-17,34%-->118,86+/-6,7%; P<0,01) and NKB (171,89+/-5, 75%-->109,5+/-4,11%; P<0,01). SR 48968 [NK(2)-antagonist] did not affect SP action, but reduced the effects of NKA and NKB. SR 142801 [NK(3)-antagonist] did not change any effect of SP, NKA or NKB. [Sar(9)]SP (NK(1)-agonist) caused strong dose-dependent secretagogue effects similar to SP, [betaAla(8)]NKA (NK(2)-agonist) showed only slight and [Pro(7)]NKB (NK(3)-agonist) no effects. The present data suggest that the secretagogue effects elicited by tachykinins in rat trachea are mediated via NK(1)receptors.
速激肽如P物质（SP）、神经激肽A（NKA）、神经激肽B（NKB）对气道黏液分泌有不同的刺激作用，在大鼠气管中的效力顺序如下：SP＞NKA＞NKB。这些不同的作用很可能是由于对速激肽受体的亲和力不同，这些受体被称为神经激肽（NK）（1）、NK（2）和NK（3）。在本研究中，我们通过选择性受体拮抗剂和受体激动剂来确定负责大鼠气管中不同促分泌作用的受体亚型。SR 140333 [NK（1）拮抗剂] 完全抑制了SP的作用（283.29±21.12%→84.53±4.09%；P＜0.01），并显著降低了NKA（179.08±17.34%→118.86±6.7%；P＜0.01）和NKB（171.89±5.75%→109.5±4.11%；P＜0.01）的作用。SR 48968 [NK（2）拮抗剂] 不影响SP的作用，但降低了NKA和NKB的作用。SR 142801 [NK（3）拮抗剂] 不改变SP、NKA或NKB的任何作用。[Sar（9）]SP（NK（1）激动剂）产生了与SP相似的强烈剂量依赖性促分泌作用，[βAla（8）]NKA（NK（2）激动剂）仅显示出轻微作用，而[Pro（7）]NKB（NK（3）激动剂）则无作用。目前的数据表明，速激肽在大鼠气管中引起的促分泌作用是通过NK（1）受体介导的。
