Djokić T D
Glas Srp Akad Nauka Med. 1992(42):107-21.
In addition to the cholinergic and adrenergic nervous systems, a new noncholinergic and nonadrenergic nervous system has recently been described, involving the afferent sensory nerves in the airways. Many irritants (dusts, chemicals) stimulate these sensory nerves to release neuropeptides. Among these neuropeptides, the "tachykinins" exist in sensory nerves of airways (substance P, neurokinin A). These tachykinins have the ability to affect multiple cells in the airways and to provoke many responses including smooth muscle contraction, mucus secretion, plasma extravasation and neutrophil adhesion. This series of effects is termed "neurogenic inflammation". Using the respiratory tract as experimental model, it has been shown that: a) substance P (SP) is widely distributed in afferent fibers in the vagus, b) SP-immunoreactivity has been demonstrated in the epithelium, in airway smooth muscle, near blood vessels and submucosal glands, c) substance P and other tachykinins are released from sensory nerve terminals during stimulation electrically and by capsaicin, d) local administration of substance P mimics the effect of sensory nerve stimulation, e) smooth muscle contraction, gland secretion and plasma leakage, normally induced by nerve stimulation or noxious stimulus, are absent in tissues pretreated with the substance P depleting agent capsaicin or with tachykinin antagonists. These findings indicate that peptidergic nerve fibers are involved in the local regulation of tone of smooth muscle, regulation of blood flow, vascular permeability, and mucus secretion. We released that degradative mechanisms could play an important role in modulating tachykinin effects, just as acetylcholinesterase modulates effects of acetylcholine released from nerve terminals. We discovered that a membrane-bound enzyme called enkephalinase (also called neutral endopeptidase, EC 3, 4, 24, 11), located on specific cells that contain tachykinin receptors, modulate the action of tachykinins by cleaving and thus inactivating them. Our studies demonstrate that viral infection or cigarette smoke potentiate various effects of tachykinins by decreasing tissue enkephalinase activity. Thus, down-regulation of enkephalinase activity in specific tissues can modify the extent of neurogenic inflammation, and this modification could be important in the pathogenesis of diseases in airways and other tissues that contain tachykinins.
除胆碱能和肾上腺素能神经系统外，最近还发现了一种新的非胆碱能和非肾上腺素能神经系统，它涉及气道中的传入感觉神经。许多刺激物（灰尘、化学物质）会刺激这些感觉神经释放神经肽。在这些神经肽中，“速激肽”存在于气道的感觉神经中（P物质、神经激肽A）。这些速激肽能够影响气道中的多种细胞，并引发许多反应，包括平滑肌收缩、黏液分泌、血浆渗出和中性粒细胞黏附。这一系列效应被称为“神经源性炎症”。以呼吸道为实验模型，研究表明：a）P物质（SP）广泛分布于迷走神经的传入纤维中；b）在上皮、气道平滑肌、血管附近和黏膜下腺体中已证实有SP免疫反应性；c）电刺激和辣椒素刺激时，P物质和其他速激肽从感觉神经末梢释放；d）局部应用P物质可模拟感觉神经刺激的效应；e）在用P物质耗竭剂辣椒素或速激肽拮抗剂预处理的组织中，通常由神经刺激或有害刺激诱导的平滑肌收缩、腺体分泌和血浆渗漏消失。这些发现表明，肽能神经纤维参与平滑肌张力的局部调节、血流调节、血管通透性调节和黏液分泌调节。我们认识到，降解机制可能在调节速激肽的作用中起重要作用，就像乙酰胆碱酯酶调节从神经末梢释放的乙酰胆碱的作用一样。我们发现一种名为脑啡肽酶（也称为中性内肽酶，EC 3, 4, 24, 11）的膜结合酶，位于含有速激肽受体的特定细胞上，通过切割并使其失活来调节速激肽的作用。我们的研究表明，病毒感染或香烟烟雾通过降低组织脑啡肽酶活性来增强速激肽的各种效应。因此，特定组织中脑啡肽酶活性的下调可改变神经源性炎症的程度，这种改变在气道和其他含有速激肽的组织的疾病发病机制中可能很重要。
