Kondo M, Tamaoki J, Takizawa T
First Department of Medicine, Tokyo Women's College, Japan.
Am Rev Respir Dis. 1990 Aug;142(2):403-6. doi: 10.1164/ajrccm/142.2.403.
We used cultured rabbit tracheal epithelium to determine the effect of mammalian-derived tachykinin on airway ciliary activity and its modulation by neutral endopeptidase EC 3.4.24.11 (NEP). Neurokinin A (NKA) caused dose-dependent increases in ciliary beat frequency (CBF), as measured by a photoelectric method, with the maximal increase from the baseline 15.7 +/- 1.7% (mean +/- SEM, p less than 0.01), whereas substance P (SP) had no effect. The NKA-induced increase in CBF was not inhibited by phentolamine, propranolol, or atropine, but it was abolished by the tachykinin antagonist [D-Pro2, D-Trp7,9]SP. Pretreatment of tissue with thiorphan (10(-5) M), a NEP inhibitor, had little effect on CBF responses to NKA; however, it significantly potentiated the responses to SP (14.9 +/- 3.0%, p less than 0.01). Other peptidase inhibitors, including captopril, bestatin, and leupeptin, did not alter the tachykinin-induced CBF response, suggesting that angiotensin converting enzyme, aminopeptidases, and serine proteinases do not modulate ciliary activity in response to tachykinins. These results suggest that NKA increases CBF by acting directly on tachykinin receptors and that NEP may play a role in modulating the tachykinin-induced stimulatory effects on CBF.
我们使用培养的兔气管上皮来确定哺乳动物来源的速激肽对气道纤毛活动的影响及其受中性内肽酶EC 3.4.24.11（NEP）的调节作用。通过光电方法测量，神经激肽A（NKA）可引起纤毛摆动频率（CBF）呈剂量依赖性增加，相对于基线的最大增加幅度为15.7 +/- 1.7%（平均值 +/- 标准误，p < 0.01），而P物质（SP）则无此作用。NKA诱导的CBF增加不受酚妥拉明、普萘洛尔或阿托品的抑制，但可被速激肽拮抗剂[D-脯氨酸2，D-色氨酸7,9]SP消除。用NEP抑制剂硫磷酰胺（10^(-5) M）预处理组织对CBF对NKA的反应影响不大；然而，它显著增强了对SP的反应（14.9 +/- 3.0%，p < 0.01）。其他肽酶抑制剂，包括卡托普利、贝司他汀和亮抑酶肽，并未改变速激肽诱导的CBF反应，这表明血管紧张素转换酶、氨肽酶和丝氨酸蛋白酶不会调节对速激肽的纤毛活动反应。这些结果表明，NKA通过直接作用于速激肽受体来增加CBF，并且NEP可能在调节速激肽诱导的对CBF的刺激作用中发挥作用。
