Kubo N, Kumazawa T
Department of Otolaryngology, Kansai Medical University, Osaka, Japan.
Acta Otolaryngol Suppl. 1993;500:97-108. doi: 10.3109/00016489309126190.
During the 1980s, our view of airway hypersensitivity was altered significantly. Advances in biochemical techniques revealed involvement of several nonspecific events in nasal hyperreactivity: Autonomic dysfunction involving primary and/or secondary receptor disorders, epithelial damage by cytotoxic proteins in eosinophil, which is stimulated by inflammatory mediators, and an axonal reflex of sensory C fibers. Since 1983, we have neurobiochemically investigated the autonomic nerve dysfunction in the nasal mucosa of patients with nasal allergy and guinea pigs with experimentally-induced nasal hypersensitivity. We propose the following mechanisms as potential contributors to the disturbance of the beta receptor function in airway hyperreactivity: i) Down-regulation caused by excess endogenous norepinephrine stimulation, ii) down-regulation and uncoupling to adenylate cyclase, produced by the inflammatory mediator-induced activation of protein kinase C, iii) the action of beta receptor inhibitory factor, presumably anti beta receptor autoantibodies, and iv) dysfunction of beta receptor kinase, which is known to cause short-term desensitization of beta receptors after exposure to beta agonists. This review provides the anatomical and neurobiochemical background for the autonomic regulation and dysfunction in the nose. We also introduce our series of experiments and the above updated hypotheses of how functional disturbances of the autonomic nerve in the nasal mucosa may occur.
在20世纪80年代，我们对气道高反应性的看法发生了显著改变。生化技术的进步揭示了鼻高反应性中几个非特异性事件的参与：涉及初级和/或次级受体紊乱的自主神经功能障碍、嗜酸性粒细胞中细胞毒性蛋白对上皮的损伤（嗜酸性粒细胞由炎症介质刺激）以及感觉C纤维的轴突反射。自1983年以来，我们从神经生化角度研究了鼻过敏患者和实验性诱导鼻高反应性豚鼠鼻黏膜中的自主神经功能障碍。我们提出以下机制可能是气道高反应性中β受体功能紊乱的潜在原因：i）内源性去甲肾上腺素过度刺激导致的下调；ii）炎症介质诱导的蛋白激酶C激活产生的下调和解偶联至腺苷酸环化酶；iii）β受体抑制因子的作用，可能是抗β受体自身抗体；iv）β受体激酶功能障碍，已知其在暴露于β激动剂后会导致β受体短期脱敏。本综述提供了鼻子自主神经调节和功能障碍的解剖学和神经生化背景。我们还介绍了我们的一系列实验以及上述关于鼻黏膜自主神经功能障碍可能如何发生的最新假说。
