FUNCTION OF PULMONARY M2 MUSCARINIC RECEPTORS IN ANTIGEN-CHALLENGED GUINEA-PIGS IS RESTORED BY HEPARIN AND POLY-L-GLUTAMATE
FUNCTION OF PULMONARY M2 MUSCARINIC RECEPTORS IN ANTIGEN-CHALLENGED GUINEA-PIGS IS RESTORED BY HEPARIN AND POLY-L-GLUTAMATE
复制标题
DOI：
10.1172/jci116116
复制
发表时间：
1992-12-01
影响因子：
15.9
通讯作者：
JACOBY, DB
中科院分区：
文献类型：
--
作者：
FRYER, AD;JACOBY, DB
在抗原激发的豚鼠中测试肝素和聚-L-谷氨酸盐对肺中副交感神经上的抑制性M2毒蕈碱自身受体的功能的影响。抗原激发后，M2受体功能下降，从而增加迷走神经释放的乙酰胆碱并增强迷走神经诱导的支气管收缩。将豚鼠麻醉、气管造口术、迷走神经切断、麻痹和通气。电刺激迷走神经引起支气管收缩和心动过缓。在对照组中，毛果芸香碱通过刺激神经元M2毒蕈碱受体减弱迷走神经诱导的支气管收缩。相反，阻断这些自身受体与gallamine增强迷走神经诱导的支气管收缩。在激发的动物中，两种药物的作用均显著降低，证实了M2受体功能障碍。肝素或聚-L-谷氨酸后20分钟，毛果芸香碱和加拉胺对迷走神经诱导的支气管收缩的作用均恢复，表明M2受体功能恢复。在对照动物中，肝素和聚-L-谷氨酸均不影响迷走神经诱导的反应。因此，抗原诱导的M2受体功能障碍可以通过聚阴离子多糖（肝素）或聚阴离子肽（聚-L-谷氨酸）逆转。这表明，多聚阳离子物质，如嗜酸性粒细胞主要碱性蛋白，阳离子蛋白，或过氧化物酶可能是负责抗原诱导的肺M2受体功能障碍。
The effect of heparin and poly-L-glutamate on the function of inhibitory M2 muscarinic autoreceptors on parasympathetic nerves in the lung was tested in antigen-challenged guinea pigs. After antigen challenge, M2 receptor function is decreased, thus increasing release of acetylcholine from the vagus and potentiating vagally induced bronchoconstriction. Guinea pigs were anesthetized, tracheostomized, vagotomized, paralyzed, and ventilated. Electrical stimulation of the vagi caused bronchoconstriction and bradycardia. In controls, pilocarpine attenuated vagally induced bronchoconstriction by stimulating neuronal M2 muscarinic receptors. Conversely, blocking these autoreceptors with gallamine potentiated vagally induced bronchoconstriction. In challenged animals the effects of both drugs were markedly reduced, confirming M2 receptor dysfunction. 20 min after heparin or poly-L-glutamate, the effects of both pilocarpine and gallamine on vagally induced bronchoconstriction were restored, demonstrating recovery of M2 receptor function. Neither heparin nor poly-L-glutamate affected vagally induced responses in control animals. Thus antigen-induced dysfunction of M2 receptors can be reversed by polyanionic polysaccharides (heparin) or polyanionic peptides (poly-L-glutamate). This suggests that a polycationic substance such as eosinophil major basic protein, cationic protein, or peroxidase may be responsible for antigen-induced pulmonary M2 receptor dysfunction.