Karlsson J A, Finney M J, Persson C G, Post C
Life Sci. 1984 Dec 24;35(26):2681-91. doi: 10.1016/0024-3205(84)90038-9.
Electrical field stimulation of guinea-pig isolated hilus bronchi induced tetrodotoxin-sensitive contractions of which only a minor part could be inhibited by atropine. The remaining non-cholinergic bronchoconstriction was antagonized by a heptapeptide and an undecapeptide substance P (SP) analogue (Arg5, D-Trp7,9) SP5-11, IC50 = 24.0 microM and (D-Pro2, D-Trp 7,9) SP, IC50 = 10.0 microM. Of the exogenously added tachykinins, both eledoisin (8 times) and physalaemin (3 times) were more potent bronchoconstrictors than SP. Pretreatment with the SP-analogues shifted concentration-response curves to the tachykinins to the right, eledoisin being most readily antagonized. (Arg5, D-Trp 7,9) SP 5-11 also antagonized the neural response more readily than that of SP. In addition, in the frog isolated sciatic nerve preparation the two SP-analogues were found to possess potent lidocaine-like neurodepressant actions which further complicated the interpretation of the neural inhibitory effects of these compounds. It is concluded that if a tachykinin contributes to non-cholinergic bronchoconstriction, an eledoisin-like peptide is a more likely candidate than SP itself. Since SP-antagonists may have local anaesthetic properties their value as tools in neurophysiology seems limited. Inferentially, the non-cholinergic bronchoconstrictive neurotransmitter remains to be identified.
电场刺激豚鼠离体肺门支气管可引起对河豚毒素敏感的收缩，其中只有一小部分可被阿托品抑制。其余的非胆碱能支气管收缩可被一种七肽和一种十一肽P物质（SP）类似物（Arg5，D-Trp7,9）SP5-11拮抗，IC50 = 24.0微摩尔，以及（D-Pro2，D-Trp 7,9）SP，IC50 = 10.0微摩尔。在外源性添加的速激肽中，eledoisin（8倍）和physalaemin（3倍）作为支气管收缩剂比SP更有效。用SP类似物预处理可使速激肽的浓度-反应曲线右移，eledoisin最容易被拮抗。（Arg5，D-Trp 7,9）SP 5-11也比SP更容易拮抗神经反应。此外，在青蛙离体坐骨神经制备中，发现这两种SP类似物具有类似利多卡因的强效神经抑制作用，这进一步使这些化合物的神经抑制作用的解释变得复杂。得出的结论是，如果一种速激肽参与非胆碱能支气管收缩，那么一种类似eledoisin的肽比SP本身更有可能是候选物。由于SP拮抗剂可能具有局部麻醉特性，它们作为神经生理学工具的价值似乎有限。由此推断，非胆碱能支气管收缩性神经递质仍有待确定。
