DYSFUNCTION OF M2-MUSCARINIC RECEPTORS IN PULMONARY PARASYMPATHETIC NERVES AFTER ANTIGEN CHALLENGE
DYSFUNCTION OF M2-MUSCARINIC RECEPTORS IN PULMONARY PARASYMPATHETIC NERVES AFTER ANTIGEN CHALLENGE
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DOI：
10.1152/jappl.1991.71.6.2255
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发表时间：
1991-12-01
影响因子：
3.3
通讯作者：
WILLSKARP, M
中科院分区：
文献类型：
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作者：
FRYER, AD;WILLSKARP, M
在麻醉豚鼠中研究了抗原激发对肺部神经元 M2-毒蕈碱自身受体功能的影响。 在第1、3和5天对豚鼠腹腔注射生理盐水（对照组）或卵清蛋白（10 mg/kg）。在第20-25天用雾化卵清蛋白攻击一组致敏动物，持续5分钟/天（攻击组），而另一组致敏动物不进行攻击（致敏组）。 第26天，对动物进行麻醉、麻痹、气管造口术和人工通气。 记录肺膨胀压（Ppi）、潮气量、血压和发热率。 两条迷走神经均被切断，远端部分的电刺激引起支气管收缩（表现为 Ppi 的增加）和心动过缓。 在对照组中，毛果芸香碱（1-100-mu-g/kg iv）通过刺激肺部副交感神经上的抑制性 M2-毒蕈碱受体来减弱迷走神经诱导的支气管收缩。 相反，用拮抗剂没食子胺（0.1-10 mg/kg iv）阻断这些受体可显着增强迷走神经诱导的支气管收缩。 这些结果证实了之前的发现。 在受攻击的豚鼠中，毛果芸香碱不抑制迷走神经诱导的支气管收缩。 此外，没食子胺并没有将迷走神经诱导的支气管收缩增强到与对照组相同的程度。 在致敏但未攻击的动物组中，没食子胺对迷走神经诱导的支气管收缩的增强作用与对照组相同。 与对照组相比，致敏或攻击动物的基线 Ppi 没有增加。 在心脏中，没食子胺对两组动物中迷走神经诱导的心动过缓的抑制作用相同，这表明，在抗原攻击的动物中，肺部副交感神经上 M2 受体功能的变化并不是 M2 受体功能普遍下降的一部分。 这些结果表明，M2-毒蕈碱受体介导的对肺部副交感神经乙酰胆碱释放的抑制在致敏动物中没有改变，但在用抗原攻击的致敏动物中减弱。 失去这种抑制作用将导致副交感神经释放乙酰胆碱增加，并可能解释抗原攻击后气道高反应性。
The effect of antigen challenge on the function of neuronal M2-muscarinic autoreceptors in the lungs was studied in anesthetized guinea pigs. Guinea pigs were injected intraperitoneally with saline (control group) or ovalbumin (10 mg/kg) on days 1, 3, and 5. One group of sensitized animals was challenged on days 20-25 with aerosolized ovalbumin for 5 min/day (challenged group), while another group of the sensitized animals was not challenged (sensitized group). On day 26 the animals were anesthetized, paralyzed, tracheostomized, and artificially ventilated. Pulmonary inflation pressure (Ppi), tidal volume, blood pressure, and heat rate were recorded. Both vagus nerves were cut, and electrical stimulation of the distal portions caused bronchoconstriction (meansured as an increase in Ppi) and bradycardia. In the control group, pilocarpine (1-100-mu-g/kg iv) attenuated vagally induced bronchoconstriction by stimulating inhibitory M2-muscarcinic receptors on parasympathetic nerves in the lungs. Conversely, blockade of these receptors with the antagonist gallamine (0.1-10 mg/kg iv) produced a marked potentiation of vagally induced bronchoconstriction. These results confirm previous findings. In the challenged guinea pigs, pilocarpine did not inhibit vagally induced bronchoconstriction. Furthermore, gallamine did not potentiate vagally induced bronchoconstriction to the same degree as in the controls. In the group of animals that was sensitized but not challenged, the potentiation of vagally induced bronchoconstriction by gallamine was identical to the controls. There was no increase in baseline Ppi in the sensitized or challenged animals compared with the controls. In the heart, gallamine inhibited vagally induced bradycardia equally in both groups of animals, indicating that, in antigen-challenged animals, changes in M2-receptor function on parasympathetic nerves in the lungs are not part of a generalized decrease in M2-receptor function. These results demonstrate that M2-muscarinic receptor-mediated inhibition of acetylcholine release from parasympathetic nerves in the lungs is not altered in sensitized animals but is decreased in sensitized animals that have been challenged with antigen. Loss of this inhibition would result in increased release of acetylcholine from the parasympathetic nerves and may explain airway hyperresponsiveness after antigen challenge.