Release of [3H]acetylcholine in human isolated bronchi. Effect of indomethacin on muscarinic autoinhibition.
Release of [3H]acetylcholine in human isolated bronchi. Effect of indomethacin on muscarinic autoinhibition.
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[3H]乙酰胆碱在人离体支气管中的释放。
DOI：
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发表时间：
1995
影响因子：
24.7
通讯作者：
K. Racké
中科院分区：
文献类型：
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作者：
I. Wessler;H. Bender;P. Härle;K. Höhle;G. Kirdorf;H. Klapproth;T. Reinheimer;J. Říčný;K. E. Schniepp;K. Racké
受体介导的调节乙酰胆碱释放的气道，特别是在人类，仍然不清楚。在本研究中，乙酰胆碱的组织含量和释放的[3 H]乙酰胆碱测定新鲜解剖的人支气管在开胸手术获得。大（主支气管和叶支气管）和小（段支气管和亚段支气管）气道含有大量内源性乙酰胆碱（300 +/- 50 pmol/100 mg湿重），而肺实质中的含量明显较少（60 +/- 30 pmol/100 mg）。在含有前体[3 H]胆碱的器官浴中孵育的离体小支气管合成了大量的[3 H]乙酰胆碱（26，000 +/-4，000 dpm/100 mg）。随后的透壁刺激（四个20秒列车在15赫兹）的放射性标记的支气管引起增强的氚流出，被取消的细胞外钙或河豚毒素。在透壁刺激之前、期间和之后收集的介质的HPLC分析表明，电刺激的氚流出仅代表[3 H]乙酰胆碱，而[3 H]胆碱和[3 H]磷酸胆碱的流出不受电刺激的影响。氧震颤素（0.1和1 μ mol/L）以浓度相关的方式抑制诱发的[3 H]乙酰胆碱释放，而阿托品（0.03 μ mol/L）增强诱发的[3 H]乙酰胆碱释放。3 μ mol/L吲哚美辛对环氧合酶活性的失活并不影响0.1或1 μ mol/L氧震颤素的抑制作用。总之，目前的实验表明，相当大的胆碱能神经支配的人类大，小气道。
Receptor-mediated regulation of acetylcholine release in the airways, particularly in humans, remains unclear. In the present study, the tissue content of acetylcholine and release of [3H]acetylcholine were measured in freshly dissected human bronchi obtained at thoracotomy. Large (main and lobar bronchi) and small (segmental and subsegmental bronchi) airways contained considerable amounts of endogenous acetylcholine (300 +/- 50 pmol/100 mg wet weight), whereas significantly less was found in lung parenchyma (60 +/- 30 pmol/100 mg). Isolated small bronchi incubated in an organ bath with the precursor [3H]choline synthesized significant amounts of [3H]acetylcholine (26,000 +/- 4,000 dpm/100 mg). Subsequent transmural stimulation (four 20 s trains at 15 Hz) of radiolabeled bronchi caused an enhanced tritium outflow that was abolished by removal of extracellular calcium or by tetrodotoxin. HPLC analysis of the medium collected before, during, and after transmural stimulation showed that the electrically stimulated tritium outflow represented exclusively [3H]acetylcholine, whereas the outflow of [3H]choline and [3H]phosphorylcholine was not affected by electrical stimulation. Oxotremorine (0.1 and 1 mumol/L) inhibited evoked [3H]acetylcholine release in a concentration-related manner, whereas atropine (0.03 mumol/L) enhanced evoked [3H]acetylcholine release. Inactivation of cyclooxygenase activity by 3 mumol/L of indomethacin did not impair the inhibitory effect of 0.1 or 1 mumol/L of oxotremorine. In conclusion, the present experiments indicate a considerable cholinergic innervation of human large and small airways.