Jinno S, Hua X Y, Yaksh T L
Department of Anesthesiology, University of California, San Diego, La Jolla 92093-0818.
J Appl Physiol (1985). 1994 Apr;76(4):1651-6. doi: 10.1152/jappl.1994.76.4.1651.
In the present study, we observed that nicotine, the nicotinic analogue cytisine, and acetylcholine (ACh) evoked a concentration-dependent (5 x 10(-6)-5 x 10(-5) M) release of calcitonin gene-related peptide (CGRP) from the rat trachea. After a prolonged exposure to capsaicin, nicotine-induced CGRP release was absent, suggesting that the release of CGRP by nicotine is derived from capsaicin-sensitive afferent terminals. Nicotine- and cytisine-induced release displayed a significant degree of tachyphylaxis after sequential exposures. The release of CGRP evoked by capsaicin was also reduced after nicotine and cytisine desensitization. This indicates that similar mechanisms may mediate the tachyphylactic effect of capsaicin and nicotine. Hexamethonium and mecamylamine blocked the effect of nicotine but not that of ACh, whereas atropine significantly attenuated the release of CGRP outflow induced by ACh. Physostigmine and neostigmine did not alter resting release of CGRP from rat trachea, although exogenous (10(-5) M) ACh-induced CGRP release was enhanced in the presence of neostigmine, suggesting minimal tonic cholinergic activity in this model. We conclude that activation of nicotinic and muscarinic receptors in the rat trachea can induce local release of CGRP. These observations indicate that cholinergically induced airway responses may be mediated in part by activation of the peripheral terminals of primary afferent sensory neurons and subsequent release of local neuropeptides.
在本研究中，我们观察到尼古丁、烟碱类似物金雀花碱和乙酰胆碱（ACh）可引起大鼠气管中降钙素基因相关肽（CGRP）浓度依赖性（5×10⁻⁶ - 5×10⁻⁵ M）的释放。在长时间暴露于辣椒素后，尼古丁诱导的CGRP释放消失，这表明尼古丁诱导的CGRP释放源自辣椒素敏感的传入神经末梢。尼古丁和金雀花碱诱导的释放在连续暴露后表现出显著程度的快速减敏。在尼古丁和金雀花碱脱敏后，辣椒素诱发的CGRP释放也减少。这表明类似的机制可能介导辣椒素和尼古丁的快速减敏效应。六甲铵和美加明阻断了尼古丁的作用，但未阻断ACh的作用，而阿托品显著减弱了ACh诱导的CGRP流出释放。毒扁豆碱和新斯的明未改变大鼠气管中CGRP的静息释放，尽管在新斯的明存在的情况下，外源性（10⁻⁵ M）ACh诱导的CGRP释放增强，这表明该模型中胆碱能张力活性最小。我们得出结论，大鼠气管中烟碱受体和毒蕈碱受体的激活可诱导CGRP的局部释放。这些观察结果表明，胆碱能诱导的气道反应可能部分由初级传入感觉神经元外周末梢的激活以及随后局部神经肽的释放介导。
