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豚鼠经神经反射介导的鼻分泌物机制及抗变态反应药物的评价

Mechanism of nasal secretion mediated via nerve reflex in guinea pigs and evaluation of antiallergic drugs.

作者信息

Namimatsu A, Go K, Tanimoto H, Okuda M

机构信息

Institute of Bio-Active Science, Nippon Zoki Pharmaceutical Company, Hyogo; Japan.

出版信息

Int Arch Allergy Immunol. 1992;97(2):139-45. doi: 10.1159/000236109.

Abstract

In order to confirm the mechanism of nasal secretion mediated via a nerve reflex in guinea pigs, the secretory response from the contralateral side was studied which was induced by local application of various stimulators. There was no difference in the nasal secretion between the contralateral and the stimulated sides when the secretion was induced by allergen, histamine, and capsaicin at lower doses. Methacholine caused a nasal secretion only on the stimulated side. Pretreatment with local anesthetic and ganglionic blockers blocked the secretory response bilaterally which was induced by allergen, histamine, and capsaicin. Antihistaminics also blocked the secretory response induced by allergen and histamine on both sides, but not the capsaicin-induced nasal secretion. Unilateral pretreatment with local anticholinergics prevented all secretory responses only on the stimulated side. Thus, exogenous and endogenous histamine released by the allergen-antibody reaction may stimulate histamine H1 receptors located in the sensory nerve endings as trigger, resulting in the secretory response mediated via a nerve reflex, while methacholine may act directly on nasal glands. Ketotifen and azelastine, which are chemical mediators releasing inhibitor with antihistaminergic activity, prevented the nasal secretion induced by histamine and allergen. On the other hand, disodium cromoglycate, amlexanox, and tranilast had only a slight effect on the allergen-induced nasal secretion. The secretory response on the contralateral side induced by various stimulators would be useful in the in vivo evaluation of anti-allergic drugs to demonstrate the difference in their modes of action.

摘要

为了证实豚鼠中通过神经反射介导的鼻分泌物机制,研究了局部应用各种刺激物诱导的对侧分泌反应。当低剂量的变应原、组胺和辣椒素诱导分泌时,对侧和刺激侧的鼻分泌物没有差异。乙酰甲胆碱仅在刺激侧引起鼻分泌物。局部麻醉药和神经节阻滞剂预处理可双侧阻断变应原、组胺和辣椒素诱导的分泌反应。抗组胺药也可阻断变应原和组胺在双侧诱导的分泌反应,但不能阻断辣椒素诱导的鼻分泌物。局部抗胆碱能药单侧预处理仅能防止刺激侧的所有分泌反应。因此,变应原-抗体反应释放的外源性和内源性组胺可能刺激位于感觉神经末梢的组胺H1受体作为触发因素,导致通过神经反射介导的分泌反应,而乙酰甲胆碱可能直接作用于鼻腺。具有抗组胺活性的化学介质释放抑制剂酮替芬和氮卓斯汀可防止组胺和变应原诱导的鼻分泌物。另一方面,色甘酸钠、氨来呫诺和曲尼司特对变应原诱导的鼻分泌物仅有轻微影响。各种刺激物在对侧诱导的分泌反应将有助于在体内评估抗过敏药物,以证明它们作用方式的差异。

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