INCREASED ACETYLCHOLINE-RELEASE IN TRACHEAS FROM ALLERGEN-EXPOSED IGE-IMMUNE MICE
INCREASED ACETYLCHOLINE-RELEASE IN TRACHEAS FROM ALLERGEN-EXPOSED IGE-IMMUNE MICE
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DOI：
10.1152/ajplung.1994.266.3.l263
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发表时间：
1994-03-01
影响因子：
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通讯作者：
GELFAND, EW
中科院分区：
文献类型：
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作者：
LARSEN, GL;FAME, TM;GELFAND, EW
在免疫球蛋白E(IgE)免疫过敏原暴露的动物中，乙酰胆碱(ACh)从呼吸道副交感神经末梢释放的增加可能是导致气道反应性增加的机制之一。我们在体外测定了电场刺激后小鼠气管释放的ACh。将BALB/c小鼠暴露于含1%卵清蛋白的无菌磷酸盐缓冲盐水气雾剂中，每天20分钟，连续10天免疫小鼠。此时，卵白蛋白特异的IgE水平按比例高于卵白蛋白特异的免疫球蛋白。作为对照，未免疫的小鼠同样单独暴露在磷酸盐缓冲盐水中。最后一次雾化48小时后，取出气管，以评估对电场刺激和胆碱能激动剂(乙酰甲胆碱或ACh)的收缩反应或电场刺激产生的ACh的释放。采用高效液相色谱-电化学检测法测定镀液中ACh的含量。非免疫组和免疫组引起一半最大收缩反应的刺激频率分别为4.1+/-0.2和2.8+/-0.2赫兹(P=0.0001)，而引起一半最大收缩反应的乙酰甲胆碱的摩尔浓度无显著差异。此外，免疫和非免疫气管对ACh的剂量-反应曲线是重叠的。免疫小鼠气管ACh释放量在10和20赫兹时均显著增加。非免疫组和免疫组小鼠气管ACh释放量在10 Hz时分别为140+/-8和205+/-22(P=0.013)，在20 Hz时分别为147+/-13和227+/-14(P=0.008)。Mt M受体拮抗剂(加拉胺)和该受体激动剂(匹罗卡品)能调节非免疫组和免疫组小鼠气管ACh的释放。这些结果表明，随着IgE反应状态的发展，反复呼吸道暴露于变应原会导致呼吸道神经控制的改变，神经末梢释放的ACh增加。这种ACh释放的增加与免疫动物气管M(2)M(2)自身受体功能的丧失有关。
Increased release of acetylcholine (ACh) from airway parasympathetic nerve endings is one mechanism that may contribute to increases in airway responsiveness in immunoglobulin E (IgE)-immune allergen-exposed animals. We measured ACh released from murine tracheas following electrical field stimulation in vitro. BALB/c mice were immunized by exposure to an aerosol of 1% ovalbumin in sterile phosphate-buffered saline for 20 min/day for 10 days. At this time, levels of ovalbumin-specific IgE were proportionately higher than oval-bumin-specific IgG. As a control, nonimmune mice were similarly exposed to phosphate-buffered saline alone. Forty-eight hours after the last aerosol, tracheas were removed for assessment of either the contractile responses to electrical field stimulation and a cholinergic agonist (methacholine or ACh) or release of ACh produced by electrical field stimulation. ACh in the bath was measured using high-performance liquid chromatography with electrochemical detection. The stimulation frequencies causing one-half the maximal contractile response to electrical field stimulation were 4.1 +/- 0.2 and 2.8 +/- 0.2 Hz (P = 0.0001) for nonimmune and immune mice, respectively, whereas the molar concentrations of methacholine causing one-half of the maximal contractile response did not significantly differ. In addition, the dose-response curves of immune and nonimmune tracheas to ACh were superimposable. A significant increase in ACh release was demonstrated at both 10 and 20 Hz in tracheas from immune mice. ACh release (pmol.g tissue(-1) min(-1)) from nonimmune and immune murine tracheas, respectively, were 140 +/- 8 and 205 +/- 22 (P = 0.013) at 10 Hz and 147 +/- 13 and 227 +/- 14 (P = 0.008) at 20 Hz, An antagonist of the Mt muscarinic autoreceptor (gallamine) and an agonist for this receptor (pilocarpine) were able to modulate ACh release from tracheas from nonimmune but not immune mice. These results suggest repeated airway exposure to allergen associated with the development of an IgE-responsive state leads to altered neural control of airways with increased release of ACh from neural terminals. This increase in ACh release was associated with loss of function of the M(2) muscarinic autoreceptor in tracheas from immune animals.