Regulation of secretion in Clara cells: studies using the isolated perfused rat lung.
Regulation of secretion in Clara cells: studies using the isolated perfused rat lung.
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克拉拉细胞分泌的调节：使用分离的灌注大鼠肺进行的研究。
DOI：
10.1172/jci110041
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发表时间：
1981
期刊：
影响因子：
--
通讯作者：
Massaro,D
中科院分区：
文献类型：
--
作者：
Massaro,GD;Fischman,CM;Chiang,MJ;Amado,C;Massaro,D
我们实验室以前的研究表明，β-肾上腺素能和胆碱能药都能刺激大鼠细支气管炎Clara细胞的体内分泌。这些研究也为一系列的β-肾上腺素能-胆碱能分泌刺激提供了支持。为了进一步探索Clara细胞分泌的调节，并在没有全身影响的情况下进行这项工作，我们使用了隔离的通风灌流大鼠肺。我们再次使用形态计量学和电子显微镜通过测量细支气管Clara细胞分泌颗粒的体积密度(细胞体积的百分比)来评估分泌。我们发现，在离体灌流肺中，异丙肾上腺素刺激Clara细胞的分泌，这种作用可被β-肾上腺素能拮抗剂心得安阻断。匹罗卡品与其在完整动物体内的作用不同，它不刺激离体肺的分泌；相反，它抑制异丙肾上腺素的分泌作用。增加潮气量通气量刺激分泌；心得安不能阻断这一作用。环(C)AMP和cGMP的类似物也刺激Clara细胞分泌。这些发现表明，至少有两种机制可以刺激Clara细胞分泌。一种似乎是β-肾上腺素能-cAMP介导的，但触发事件尚不清楚。另一种是由潮气量增加引起的，cGMP可能参与了这种刺激性事件的细胞内调节。最后，我们发现在Clara细胞的分泌调节中存在β-肾上腺素能(刺激性)-胆碱能(抑制性拮抗)的证据。
Previous studies from our laboratory indicated that both beta-adrenergic and cholinergic agents stimulate in vivo secretion by rat bronchiolar Clara cells. Those studies also provided support for an in-series beta-adrenergic-cholinergic stimulation of secretion. To further explore the regulation of secretion in Clara cells, and to do it in the absence of systemic influences, we have used the isolated ventilated perfused rat lung. We have again used morphometry and electron microscopy to assess secretion by measuring the volume density (fraction of cell volume) of the secretory granules of bronchiolar Clara cells. We found that in the isolated perfused lung, as in the intact animal, isoproterenol stimulated secretion in Clara cells and that this effect was blocked by the beta-adrenergic antagonist propranolol. Pilocarpine, unlike its action in the intact animal, did not stimulate secretion in the isolated lung; rather it inhibited the secretory effect of isoproterenol. Increased tidal-volume ventilation stimulated secretion; propranolol did not block this effect. Analogs of cyclic (c)AMP and of cGMP also stimulated secretion by Clara cells. These findings indicate that there are at least two mechanisms by which Clara cells can be stimulated to secrete. One seems to be beta-adrenergic-cAMP mediated but the triggering event is unknown. The other is initiated by increased tidal volume and cGMP may be involved in the intracellular mediation of this stimulatory event. Finally, we found evidence of beta-adrenergic (stimulatory) -cholinergic (inhibitory antagonism in the regulation of secretion in Clara cells.