Martling C R, Saria A, Fischer J A, Hökfelt T, Lundberg J M
Department of Anaesthesia, Karolinska Institute, Stockholm, Sweden.
Regul Pept. 1988 Feb;20(2):125-39. doi: 10.1016/0167-0115(88)90046-8.
The occurrence and distribution of calcitonin gene-related peptide (CGRP) in the lower airways was studied by means of immunohistochemistry and radioimmunoassay (RIA) in combination with high performance liquid chromatography (HPLC). CGRP-like immunoreactivity (-LI) was observed in nerves from the epiglottis down to peripheral bronchi in rat, cat and guinea pig and also in human bronchi. Double staining revealed colocalization of CGRP-LI and substance P (SP)-LI in cell bodies of nodose and jugular ganglia as well as in axons and nerve terminals of the airways. Systemic capsaicin pretreatment induced a marked loss of the CGRP- and SP-immunoreactive (-IR) nerves in the lower airways. CGRP-IR was also present in epithelial endocrine cells and neuroepithelial bodies. The content of CGRP-LI as measured with RIA in guinea pig bronchi was significantly lower after capsaicin pretreatment. Analysis of human bronchial extracts revealed that CGRP-LI coeluted with synthetic human CGRP on HPLC. In the isolated perfused guinea pig lung capsaicin exposure caused overflow of CGRP-LI suggesting release from peripheral branches of sensory nerves. Both in vivo experiments in the guinea pig measuring insufflation pressure as well as in vitro studies on isolated guinea pig and human bronchi showed that whereas tachykinins contracted bronchial smooth muscle no contractile or relaxing effect was elicited by human or rat CGRP. However, CGRP caused relaxation of serotonin precontracted guinea pig and human pulmonary arteries. In conclusion, the presence and release of CGRP-LI from capsaicin sensitive nerves in the lower airways adds another possible mediator, in addition to tachykinins, of vascular reactions upon sensory nerve irritation.
采用免疫组织化学、放射免疫分析法（RIA）并结合高效液相色谱法（HPLC），研究降钙素基因相关肽（CGRP）在下呼吸道的发生及分布情况。在大鼠、猫和豚鼠从会厌至外周支气管的神经中以及人类支气管中均观察到CGRP样免疫反应性（-LI）。双重染色显示，CGRP-LI与P物质（SP）-LI共定位在结状神经节和颈静脉神经节的细胞体以及气道的轴突和神经末梢中。全身辣椒素预处理导致下呼吸道中CGRP和SP免疫反应性（-IR）神经显著减少。CGRP-IR也存在于上皮内分泌细胞和神经上皮小体中。辣椒素预处理后，用RIA法测定的豚鼠支气管中CGRP-LI含量显著降低。对人支气管提取物的分析表明，CGRP-LI在HPLC上与合成的人CGRP共洗脱。在分离的灌注豚鼠肺中，辣椒素暴露导致CGRP-LI溢出，提示其从感觉神经的外周分支释放。在豚鼠体内测量吹入压力的实验以及对分离的豚鼠和人支气管的体外研究均表明，速激肽可使支气管平滑肌收缩，而人或大鼠CGRP未引起收缩或舒张作用。然而，CGRP可使5-羟色胺预收缩的豚鼠和人肺动脉舒张。总之，下呼吸道中辣椒素敏感神经释放CGRP-LI，这除了速激肽外，为感觉神经刺激时血管反应增加了另一种可能的介质。
