Bertrand C, Geppetti P, Graf P D, Foresi A, Nadel J A
Cardiovascular Research Institute, University of California, San Francisco 94143-0130.
Am J Physiol. 1993 Nov;265(5 Pt 1):L507-11. doi: 10.1152/ajplung.1993.265.5.L507.
The role of tachykinins released from sensory nerves in bronchoconstriction induced by antigen was studied in sensitized guinea pigs anesthetized with pentobarbital sodium and pretreated with atropine. The combination of NK2 (SR-48968) and NK1 (CP-96,345) tachykinin-receptor antagonists abolished the increase in total pulmonary resistance (RL) evoked by intravenous capsaicin but did not affect the response evoked by intravenous histamine. A small dose of aerosolized ovalbumin (OVA, 0.1%) produced a small increase in RL that was further increased and markedly prolonged by the neutral endopeptidase (NEP) inhibitor phosphoramidon; this bronchoconstrictor effect of OVA was markedly reduced by the NK2-receptor antagonist and was abolished by the combination of the NK1 and NK2-receptor antagonists together. When a larger dose of OVA (0.5%) was used, a maximal bronchoconstrictor response was obtained. Phosphoramidon did not potentiate this response significantly. The combination of NK1- and NK2-receptor antagonists blunted the response at 5 min only slightly but markedly attenuated the later (10-20 min) response. These results show that tachykinins released from sensory nerves play a significant role in antigen-induced bronchoconstriction in guinea pigs. This effect is exaggerated when the normal modulation of neuropeptides by NEP is inhibited and is mediated predominantly by NK2-receptor activation, with a smaller contribution by NK1 receptors.
在戊巴比妥钠麻醉并用阿托品预处理的致敏豚鼠中，研究了感觉神经释放的速激肽在抗原诱导的支气管收缩中的作用。NK2（SR - 48968）和NK1（CP - 96,345）速激肽受体拮抗剂的联合使用消除了静脉注射辣椒素引起的总肺阻力（RL）增加，但不影响静脉注射组胺引起的反应。小剂量雾化卵清蛋白（OVA，0.1%）使RL有小幅增加，中性内肽酶（NEP）抑制剂磷酰胺素可使其进一步增加并显著延长；OVA的这种支气管收缩作用被NK2受体拮抗剂显著降低，并被NK1和NK2受体拮抗剂联合使用完全消除。当使用较大剂量的OVA（0.5%）时，可获得最大支气管收缩反应。磷酰胺素并未显著增强此反应。NK1和NK2受体拮抗剂联合使用仅在5分钟时轻微减弱反应，但显著减弱后期（10 - 20分钟）的反应。这些结果表明，感觉神经释放 的速激肽在豚鼠抗原诱导的支气管收缩中起重要作用。当NEP对神经肽的正常调节被抑制时，这种作用会被放大，且主要由NK2受体激活介导，NK1受体的作用较小。
