Takeda N
Department of Otolayngology, Osaka University Medical School, Japan.
Nihon Kyobu Shikkan Gakkai Zasshi. 1993 Dec;31 Suppl:108-14.
The role of neuropeptides in nasal hyperreactivity was examined in guinea pigs by histochemical and pharmacological study. Intranasal application of toluene diisocynate (TDI) induced nasal hyperreactivity symptoms: sneezing and watery rhinorrhea, and decreased histamine content in the nasal mucosa in guinea pigs sensitized with TDI. The immunoreactivity of substance P (SP) and calcitonin gene-related peptide (CGRP) in the nerve terminals in the nasal mucosa was increased after intranasal application of TDI. We also observed a decrease in the immunoreactivity of SP and CGRP, and an increase in their mRNA expression in trigeminal ganglion neurons. These findings indicate that exposure to TDI enhanced the biosynthesis of both SP and CGRP in the trigeminal ganglion neurons and their axonal transportation to the terminals in the nasal mucosa. In animals pretreated with capsaicin before sensitization, TDI did not induce nasal allergy-like behavior and histamine release in the nasal mucosa. Since capsaicin depletes SP and CGRP in the sensory nerves, this finding indicates neuropeptide-mediated histamine release in the nasal mucosa. All these findings suggest that, on exposure to TDI, the antidromic release of SP and CGRP in the nasal mucosa triggers the release of histamine, resulting in the development of symptom of nasal hyperreactivity.
通过组织化学和药理学研究，在豚鼠中检测了神经肽在鼻高反应性中的作用。经鼻应用甲苯二异氰酸酯（TDI）可诱发鼻高反应性症状：打喷嚏和水样鼻漏，并降低了用TDI致敏的豚鼠鼻黏膜中的组胺含量。经鼻应用TDI后，鼻黏膜神经末梢中P物质（SP）和降钙素基因相关肽（CGRP）的免疫反应性增强。我们还观察到三叉神经节神经元中SP和CGRP的免疫反应性降低，而它们的mRNA表达增加。这些发现表明，暴露于TDI可增强三叉神经节神经元中SP和CGRP的生物合成及其向鼻黏膜末梢的轴突运输。在致敏前用辣椒素预处理的动物中，TDI不会诱发鼻黏膜的鼻过敏样行为和组胺释放。由于辣椒素会耗尽感觉神经中的SP和CGRP，这一发现表明神经肽介导了鼻黏膜中的组胺释放。所有这些发现表明，暴露于TDI时，鼻黏膜中SP和CGRP的逆向释放会触发组胺释放，从而导致鼻高反应性症状的出现。
