Goel V, Biggs D F
Life Sci. 1987 Mar 9;40(10):1007-15. doi: 10.1016/0024-3205(87)90318-3.
The effects of three tachykinins [substance P (SP), physalaemin (PH), and eledoisin-related peptide (ERP)] were investigated in anesthetized paralyzed guinea pigs. We measured airway resistance (R) and dynamic thoracic elastance (E) with a computerized technique, and blood pressure via a carotid artery. Tachykinins injected iv or intra-aortically (ia) induced dose-dependent increases in R and E, 4 times greater on iv than ia injection. They did not give rise to tachyphylaxis. As a bronchoconstrictor, PH was 5.0X and ERP 1.8X more potent than SP; time to peak response was longer for PH than for ERP and SP; and hypotensive responses, which were of similar magnitude for all three substances, lasted longest after PH. Bronchoconstrictor responses were unaltered by bilateral vagotomy, atropine, mecamylamine, and mepyramine. Morphine reduced PH-induced increases in R (P less than 0.01) and E (P less than 0.05), which were not reversed by naloxone, and capsaicin treatment 1 week before the experiments reduced both SP- and PH-induced increases in E (P less than 0.05). [D-Pro2,D-Trp7,9]-SP reduced ERP-induced increases in R and E, and [D-Arg1,D-Pro2,D-Trp7,9,Leu11]-SP reduced both SP- and PH-induced increases in R and E. We conclude that PH is the most potent bronchoconstrictor of the tachykinins tested. Tachykinin-induced bronchospasm is 'non-reflex' arising via a direct effect on airway smooth muscle; the release of histamine, acetylcholine, or other tachykinins is not involved in the responses. [D-Pro2,D-Trp7,9]-SP is more effective at SP-E receptors, and [D-Arg1,D-Pro2,D-Trp7,9,Leu11]-SP at SP-P receptors; both types of receptor are located all along the airways.
在麻醉的麻痹豚鼠中研究了三种速激肽[P物质(SP)、雨蛙肽(PH)和eledoisin相关肽(ERP)]的作用。我们用计算机技术测量气道阻力(R)和动态胸壁弹性(E)，并通过颈动脉测量血压。静脉注射或主动脉内注射速激肽可引起R和E剂量依赖性增加，静脉注射的增幅比主动脉内注射大4倍。它们不会引起快速耐受性。作为支气管收缩剂，PH的效力比SP高5.0倍，ERP比SP高1.8倍；PH达到反应峰值的时间比ERP和SP长；三种物质的降压反应幅度相似，PH后的降压反应持续时间最长。双侧迷走神经切断术、阿托品、美加明和甲氧苄二胺不改变支气管收缩反应。吗啡可降低PH引起的R增加(P<0.01)和E增加(P<0.05)，且纳洛酮不能逆转这种作用，实验前1周用辣椒素处理可降低SP和PH引起的E增加(P<0.05)。[D-Pro2,D-Trp7,9]-SP可降低ERP引起的R和E增加，[D-Arg1,D-Pro2,D-Trp7,9,Leu11]-SP可降低SP和PH引起的R和E增加。我们得出结论，PH是所测试的速激肽中最有效的支气管收缩剂。速激肽诱导的支气管痉挛是通过对气道平滑肌的直接作用产生的“非反射性”痉挛；组胺、乙酰胆碱或其他速激肽的释放不参与该反应。[D-Pro2,D-Trp7,9]-SP对SP-E受体更有效，[D-Arg1,D-Pro2,D-Trp7,9,Leu11]-SP对SP-P受体更有效；这两种受体均沿气道全程分布。
