OCCURRENCE, DISTRIBUTION AND ONTOGENY OF CGRP IMMUNOREACTIVITY IN THE RAT LOWER RESPIRATORY-TRACT - EFFECT OF CAPSAICIN TREATMENT AND SURGICAL DENERVATIONS

OCCURRENCE, DISTRIBUTION AND ONTOGENY OF CGRP IMMUNOREACTIVITY IN THE RAT LOWER RESPIRATORY-TRACT - EFFECT OF CAPSAICIN TREATMENT AND SURGICAL DENERVATIONS
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DOI:
10.1016/0306-4522(86)90285-x
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发表时间:
1986-10-01
期刊:
影响因子:
3.3
通讯作者:
POLAK, JM
POLAK, JM
中科院分区:
医学3区
文献类型:
--
作者:
CADIEUX, A;SPRINGALL, DR;POLAK, JM

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用免疫细胞化学和放射免疫法,用兔抗大鼠降钙素基因相关肽(CGRP)抗体,研究了CGRP在大鼠呼吸道内的分布和分布。在呼吸道各部均可检测到大量的CGRP免疫反应阳性物质(5-37pmoL/g),以干支气管处最高。可提取的CGRP免疫反应的凝胶过滤层析显示一个单峰,在合成的大鼠CGRP的位置洗脱。CGRP免疫反应定位于从喉到周围肺的粘膜内分泌细胞和神经纤维。CGRP免疫反应阳性的内分泌细胞仅见于气管、干支气管组和肺内气道。它们出现在妊娠后期(17天),近足月达到最大数量,出生后减少,到出生后第21天维持与成年动物相似的数量。类似地,CGRP免疫反应神经纤维在妊娠第18天首次被发现,并在出生后第21天达到成年分布。降钙素基因相关肽免疫反应神经纤维分布于平滑肌、浆膜粘液腺、呼吸道上皮下、上皮内及血管周围。CGRP也见于感觉神经节和喉肌肉系统的运动终板。新生儿经辣椒素处理后,呼吸道神经纤维的CGRP免疫反应性显著降低,肺内含CGRP的内分泌细胞数量减少不那么明显。运动终板免疫染色未见变化。迷走神经结扎实验表明,在迷走神经内行走的CGRP免疫反应神经纤维主要来自颈静脉神经节内的神经元。迷走神经右侧迷走神经结扎后,气管CGRP免疫反应神经和同侧干支气管壁明显丢失,而周围肺未见明显改变。相反,左侧迷走神经结扎引起同侧肺和支气管CGRP免疫反应神经减少,但不影响气管中的肽含量。结扎左侧迷走神经后,肺内CGRP免疫反应阳性的内分泌细胞的染色强度和数量均明显增加。我们的结论是,CGRP免疫反应在神经纤维和内分泌细胞中都有分布,并且主要与呼吸道的传入(感觉神经)神经支配有关。辣椒素治疗和迷走神经结扎后CGRP免疫反应阳性的内分泌细胞群的明显变化表明,这些细胞可能受到神经元的影响。
The occurrence and distribution of calcitonin gene-related peptide (CGRP) immunoreactivity in the rat respiratory tract were investigated by means of immunocytochemistry and radioimmunoassay using antibodies raised in rabbits to synthetic rat CGRP. Substantial amounts of CGRP immunoreactivity (range 5-37 pmol/g) were detected in all parts of the respiratory tract, the highest being in the stem bronchus. Gel filtration chromatography of extractable CGRP immunoreactivity revealed one single peak, eluting at the position of synthetic rat CGRP. CGRP immunoreactivity was localized both in mucosal endocrine cells and nerve fibers from the larynx down to the peripheral lung. CGRP-immunoreactive endocrine cells were found singly in trachea and stem bronchi and in groups in intrapulmonary airways. They appeared at a late stage of gestation (17 days), reached a maximum number near term and decreased after birth to maintain a population similar to that of the adult animals by postnatal day 21. Similarly, CGRP-immunoreactive nerve fibres were first identified by day 18 of the gestation period and reached the adult distribution of postnatal day 21. CGRP-immunoreactive nerve fibres were localized among smooth muscle, seromucous glands, beneath and within the epithelium of the airways and around blood vessels. CGRP was also found in sensory ganglia and in motor end plates of the larynx musculature. Neonatal pretreatment with capsaicin caused a marked reduction in CGRP immunoreactivity of nerve fibres in the respiratory tracts as well as a less marked decrease in the population of CGRP-containing endocrine cells of the lung. No change was seen in motor end plates immunostaining. Vagal ligation experiments revealed that CGRP-immunoreactive nerve fibres travelling in the vagus originate mainly from neurons located in the jugular ganglion. Infranodosal right vagal ligation induced a marked loss in CGRP-immunoreactive nerves of the tracheal, and of the ipsilateral stem bronchus, but no changes were observed in peripheral lung. By contrast infranodosal left side vagal ligation caused a decrease in CGRP-immunoreactive nerves of the ipsilateral lung and bronchus without affecting the peptide content in the trachea. Left vagal ligation also induced a marked increase in both the intensity of staining and number of CGRP-immunoreactive endocrine cells in the lung. We conclude that CGRP immunoreactivity is localized in both nerve fibres and endocrine cells and is associated principally with the afferent (sensory) innervation of the respiratory tract. The apparent changes in the CGRP-immunoreactive endocrine cell population following capsaicin treatment and vagal ligation suggest that these cells may be under neuronal influence.