Bongianni Fulvia, Mutolo Donatella, Cinelli Elenia, Pantaleo Tito
Dipartimento di Scienze Fisiologiche, Universita' degli Studi di Firenze, Viale G.B. Morgagni 63, I-50134 Firenze, Italy.
Eur J Neurosci. 2008 Jun;27(12):3233-43. doi: 10.1111/j.1460-9568.2008.06295.x. Epub 2008 Jun 1.
The respiratory role of neurokinin (NK) receptors was investigated in alpha-chloralose-urethane-anaesthetized, vagotomized, paralysed and artificially ventilated rabbits by using bilateral microinjections (30-50 nL) of NK receptor agonists and antagonists. Microinjections were performed in a region located just caudal to the rostral expiratory neurons. This region displayed features similar to those of the pre-Bötzinger complex (pre-BötC) of adult cats and rats, and proved to produce excitatory respiratory effects in response to microinjections of D,L-homocysteic acid. We used as agonists (0.1, 0.5 and 5 mM) substance P (SP), the NK1 receptor agonists [Sar(9), Met(O2)(11)]-SP and GR 73632, the NK2 receptor agonist NKA, the NK3 receptor agonist senktide, and as antagonists (5 mM) the NK1 receptor antagonist CP-99,994 and the NK2 receptor antagonist MEN 10376. SP always increased respiratory frequency, but NK1 receptor agonists did not change respiratory variables. NKA and senktide at 5 mm increased respiratory frequency. CP-99,994 caused increases in respiratory frequency and did not antagonize the effects of SP. MEN 10376 prevented the respiratory responses induced by NKA and reduced those provoked by SP. SP or the NK1 receptor agonists (5 mM) injected (1 microL) into the IV ventricle caused marked excitatory effects on respiration. The results suggest that NK2 and NK3, but not NK1, receptors are involved in the excitatory modulation of inspiratory activity within the investigated region and are consistent with the notion that the pre-BötC neurons are important components of the inspiratory rhythm-generating mechanisms.
通过对用α-氯醛糖-乌拉坦麻醉、切断迷走神经、麻痹并人工通气的家兔进行双侧微量注射（30 - 50 nL）神经激肽（NK）受体激动剂和拮抗剂，研究了NK受体的呼吸作用。微量注射在紧靠延髓呼气神经元头端尾侧的区域进行。该区域表现出与成年猫和大鼠的前包钦格复合体（pre - BötC）相似的特征，并且已证明对微量注射D，L - 高半胱氨酸有兴奋呼吸的作用。我们使用的激动剂（0.1、0.5和5 mM）有P物质（SP）、NK1受体激动剂[Sar(9)，Met(O2)(11)] - SP和GR 73632、NK2受体激动剂神经激肽A（NKA）、NK3受体激动剂森克肽，拮抗剂（5 mM）有NK1受体拮抗剂CP - 99,994和NK2受体拮抗剂MEN 10376。SP总是增加呼吸频率，但NK1受体激动剂不改变呼吸变量。5 mM的NKA和森克肽增加呼吸频率。CP - 99,994导致呼吸频率增加，并且不拮抗SP的作用。MEN 10376阻止了NKA诱导的呼吸反应并减弱了SP引起的反应。将SP或NK1受体激动剂（5 mM）（1 μL）注入脑室对呼吸有明显的兴奋作用。结果表明，在所研究区域内，NK2和NK3受体而非NK1受体参与吸气活动的兴奋调节，这与pre - BötC神经元是吸气节律产生机制的重要组成部分这一观点一致。
