Berner J, Shvarev Y, Lagercrantz H, Bilkei-Gorzo A, Hökfelt T, Wickström R
Department of Woman and Child Health, Karolinska Institutet, Stockholm, Sweden.
J Appl Physiol (1985). 2007 Aug;103(2):552-9. doi: 10.1152/japplphysiol.01389.2006. Epub 2007 May 24.
Substance P is known to be involved in respiratory rhythm and central pattern-generating mechanisms, especially during early development. We therefore studied respiratory responses in transgenic newborn mice (Tac1(-/-)) lacking substance P and neurokinin A (NKA). In vivo, the effects of intermittent isocapnic hypoxia (IH) and hypercapnia were studied using whole body flow plethysmography at P2-3 and P8-10. In vitro, anoxic responses and the effects of hypocapnic and hypercapnic conditions were studied in brain stem-spinal cord preparations (C4 activity) at P2. Hypoxic challenge considerably modified the respiratory activity in transgenic mice displayed in vivo as an attenuated increase in tidal volume during IH. Transgenic mice also showed a more prominent posthypoxic frequency decline in vivo, and posthypoxic neuronal arrests appeared more often in vitro. We recognized two types of sigh activity: with or without a following pause. During IH, the amount of sighs with a pause decreased and those without increased, a redistribution that became stronger with age only in controls. Intermittent anoxia induced long-term facilitation effects in controls, but not in Tac1(-/-) animals, manifested as an increase in burst frequency in vitro and by an augmentation of ventilation during posthypoxic periods in vivo. Thus our data demonstrate that a functional substance P/NKA system is of great importance for the generation of an adequate respiratory response to hypoxic provocation in newborn mice and during early maturation. It also indicates that substance P (and/or NKA) is involved in the development of the plasticity of the respiratory system.
已知P物质参与呼吸节律和中枢模式生成机制，尤其是在早期发育过程中。因此，我们研究了缺乏P物质和神经激肽A（NKA）的转基因新生小鼠（Tac1(-/-)）的呼吸反应。在体内，使用全身血流体积描记法在出生后第2 - 3天和第8 - 10天研究间歇性等碳酸血症性缺氧（IH）和高碳酸血症的影响。在体外，在出生后第2天的脑干 - 脊髓制备物（C4活性）中研究缺氧反应以及低碳酸血症和高碳酸血症条件的影响。缺氧刺激显著改变了转基因小鼠体内的呼吸活动，表现为IH期间潮气量增加减弱。转基因小鼠在体内还表现出更明显的缺氧后频率下降，并且在体外缺氧后神经元停滞更常出现。我们识别出两种类型的叹息活动：有或没有随后的暂停。在IH期间，伴有暂停的叹息量减少，无暂停的叹息量增加，这种重新分布仅在对照组中随年龄增长而增强。间歇性缺氧在对照组中诱导长期易化效应，但在Tac1(-/-)动物中未诱导，表现为体外爆发频率增加以及体内缺氧后时期通气增强。因此，我们的数据表明功能性P物质/NKA系统对于新生小鼠在缺氧刺激时产生适当的呼吸反应以及在早期成熟过程中非常重要。这也表明P物质（和/或NKA）参与呼吸系统可塑性的发育。
