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P物质和降钙素基因相关肽(CGRP)对豚鼠鼻黏膜活体分泌的影响。

Effects of substance P and calcitonin gene related peptide (CGRP) on guinea pig nasal mucosal secretion in vivo.

作者信息

Gawin A Z, Baraniuk J N, Kaliner M A

机构信息

Allergic Diseases Section, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892.

出版信息

Acta Otolaryngol. 1993 Jul;113(4):533-9. doi: 10.3109/00016489309135859.

DOI:10.3109/00016489309135859
PMID:7691022
Abstract

Trigeminal sensory nerves contain and release the neurotransmitters substance P (SP) and calcitonin gene related peptide (CGRP) in nasal mucosa. The effects of SP and CGRP on nasal secretion were tested in an in vivo model of guinea pig nasal mucosal secretion by topically applying the peptides directly to turbinates, and then lavaging the nostrils 10 min later. Concentrations of total protein, albumin, and 125I-bovine serum albumin (25I-BSA, injected intravenously at time 0 of the studies) were measured in lavage fluid. SP (beginning at 10(-8) M) and CGRP (beginning at 10(-6) M) stimulated the secretion of 125I-BSA indicating stimulation of plasma protein exudation. SP and CGRP increased total protein concentration at 10(-6) M indicating stimulation of glandular secretion. Topically applied thiorphan (1 microgram), an inhibitor of neutral endopeptidase, did not potentiate the maximal response to SP. However, thiorphan significantly prolonged the duration of 125I-BSA, total protein, and albumin secretion in response to SP indicating that the vascular and glandular responses were enhanced. This implies the presence of neutral endopeptidase, and demonstrates a regulatory role for this enzyme in vivo. These findings are consistent with the concept that SP and CGRP released by nociceptive sensory nerve axon responses in guinea pig nasal mucosa lead to plasma extravasation, albumin exudation, and glandular secretion, and that these mechanisms contribute to nasal responses to injury in this species.

摘要

三叉神经感觉神经在鼻黏膜中含有并释放神经递质P物质(SP)和降钙素基因相关肽(CGRP)。通过将这些肽直接局部应用于鼻甲,然后在10分钟后冲洗鼻孔,在豚鼠鼻黏膜分泌的体内模型中测试了SP和CGRP对鼻分泌物的影响。在冲洗液中测量总蛋白、白蛋白和125I-牛血清白蛋白(在研究的0时刻静脉注射)的浓度。SP(从10^(-8) M开始)和CGRP(从10^(-6) M开始)刺激了125I-牛血清白蛋白的分泌,表明刺激了血浆蛋白渗出。SP和CGRP在10^(-6) M时增加了总蛋白浓度,表明刺激了腺体分泌。局部应用的硫磷酰胺(1微克),一种中性内肽酶抑制剂,并没有增强对SP的最大反应。然而,硫磷酰胺显著延长了对SP反应的125I-牛血清白蛋白、总蛋白和白蛋白分泌的持续时间,表明血管和腺体反应增强。这意味着存在中性内肽酶,并证明了该酶在体内的调节作用。这些发现与以下概念一致,即豚鼠鼻黏膜中伤害性感觉神经轴突反应释放的SP和CGRP导致血浆外渗、白蛋白渗出和腺体分泌,并且这些机制有助于该物种对损伤的鼻反应。

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