White S R, Hershenson M B, Sigrist K S, Zimmermann A, Solway J
Department of Medicine, University of Chicago IL 60637.
Am J Respir Cell Mol Biol. 1993 Jun;8(6):592-6. doi: 10.1165/ajrcmb/8.6.592.
Calcitonin gene-related peptide (CGRP) is contained within and secreted by nerves and neuroepithelial bodies in the airway epithelium. To determine whether CGRP is mitogenic for airway epithelial cells, tracheal epithelial cells isolated from 26 guinea pigs were grown in primary culture for 2 days. Subconfluent cells were exposed to 10(-13) to 10(-9) M CGRP for 4 h and then returned to CGRP-free medium. Proliferation was quantified by direct cell count and by measurement of fractional labeling with the thymidine analog, bromodeoxyuridine (BrdU). CGRP exposure increased both cell number (53,980 +/- 9,870 cells after 10(-9) M CGRP versus 33,910 +/- 5,150 cells after control, P < 0.05) and fractional BrdU labeling (12.9 +/- 2.2% after 10(-11) M CGRP versus 3.9 +/- 0.9%, control; P < 0.01, n = 9) at 24 h after exposure. The mitogenic effect of CGRP persisted at least 3 days after exposure. CGRP-induced proliferation was attenuated by co-incubation with the CGRP receptor antagonist, hCGRP-(8-37). These data demonstrate that CGRP causes proliferation of guinea pig tracheal epithelial cells in primary culture through stimulation of a specific receptor, and suggest a role for this neuropeptide in regulating airway epithelial cell growth.
降钙素基因相关肽（CGRP）存在于气道上皮的神经和神经上皮小体中并由其分泌。为了确定CGRP对气道上皮细胞是否具有促有丝分裂作用，从26只豚鼠分离出的气管上皮细胞进行原代培养2天。亚汇合细胞暴露于10^(-13)至10^(-9) M的CGRP中4小时，然后再回到不含CGRP的培养基中。通过直接细胞计数和用胸苷类似物溴脱氧尿苷（BrdU）测量标记分数来量化增殖。暴露于CGRP后24小时，细胞数量增加（10^(-9) M CGRP处理后为53,980±9,870个细胞，而对照后为33,910±5,150个细胞，P<0.05），BrdU标记分数也增加（10^(-11) M CGRP处理后为12.9±2.2%，对照为3.9±0.9%；P<0.01，n = 9）。CGRP的促有丝分裂作用在暴露后至少持续3天。与CGRP受体拮抗剂hCGRP-(8-37)共同孵育可减弱CGRP诱导的增殖。这些数据表明，CGRP通过刺激特定受体导致原代培养的豚鼠气管上皮细胞增殖，并提示这种神经肽在调节气道上皮细胞生长中起作用。
