Muscarinic stimulation of submucosal glands in swine trachea.
Muscarinic stimulation of submucosal glands in swine trachea.
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猪气管粘膜下腺的毒蕈碱刺激。
DOI：
10.1152/jappl.1988.64.1.200
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
Dwyer,TM
中科院分区：
文献类型：
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作者：
Yang,CM;Farley,JM;Dwyer,TM
以[3H]苄基喹啉酯（[3H]QNB）和N-[3H]甲基东莨菪碱（[3H]NMS）为配体，测定了毒毒碱乙酰胆碱受体（mAChR）在气管外植体和离体粘膜下腺细胞上的特性。吡仑西平对([3H]NMS结合的竞争性位移分析表明，M1-(27 +/- 2%)和M2G-(73 +/- 2%)受体在对照组离体气管粘膜下腺细胞（TSGC’s）上存在。每日给予二异丙基氟磷酸（DFP）抑制胆碱酯酶活性95%以上。DFP处理7天后，[3H]QNB与完整TSGC的结合从14.2 +/- 0.6下降到6.3 +/- 0.8 fmol/10(6)个细胞；同样，[3H]NMS结合从8.1 +/- 1.9下降到2.0 +/- 0.8 fmol/10(6)个细胞。其中以M2G亚型的缺失居多，相对比例降至33%。此外，90%的受体对[3H]NMS的碳醇置换呈高亲和状态。通过测定气管粘膜下腺体外植体和离体细胞中3h标记的黏液大分子的释放量来定量黏液分泌。2 × 10(-5) M的乙酰胆碱（ACh）分别使黏液分泌量增加2.5倍和2.3倍。DFP消除乙酰胆碱酯酶（AChe）可使乙酰胆碱酯酶敏感性提高18倍和5倍。体内DFP处理2小时后获得的气管外植体或TSGC显示出6倍和3倍的乙酰胆碱刺激。在继续每日给药DFP期间，这种乙酰胆碱敏感性下降，因此在治疗7天后，乙酰胆碱的刺激仅为1.3倍和1.1倍。（摘要删节250字）
The properties of muscarinic acetylcholine receptors (mAChR) on tracheal explants and isolated submucosal gland cells were determined using [3H]quinuclidinyl benzilate ([3H]QNB) and N-[3H]methylscopolamine ([3H]NMS) as ligands. Analysis of competitive displacement of ([3H]NMS binding by pirenzepine demonstrated the presence of M1- (27 +/- 2%) and M2G- (73 +/- 2%) receptors on isolated tracheal submucosal gland cells (TSGC's) in control. Daily administration of diisopropylfluorophosphate (DFP) inhibited cholinesterase activity by greater than 95%. After 7 days of DFP treatment, [3H]QNB binding to intact TSGC's decreased from 14.2 +/- 0.6 to 6.3 +/- 0.8 fmol/10(6) cells; similarly, [3H]NMS binding fell from 8.1 +/- 1.9 to 2.0 +/- 0.8 fmol/10(6) cells. The loss of mAChR's was predominantly of the M2G subtype with the relative proportion dropping to 33%. In addition, 90% of the receptors assumed the high-affinity state for carbachol displacement of [3H]NMS. Mucus secretion was quantitated by measuring the release of 3H-labeled mucus macromolecules from explants of tracheal submucosal glands and isolated cells. Acetylcholine (ACh), 2 X 10(-5) M, stimulated mucus secretion by 2.5 and 2.3 times the basal rate, respectively. Elimination of acetylcholinesterase (AChe) by DFP increased the ACh sensitivity by 18- and 5-fold. Tracheal explants or TSGC's obtained 2 h after an in vivo DFP treatment showed a 6- and 3-fold ACh stimulation. This ACh sensitivity decreased during the continued daily dosing with DFP such that only a 1.3- and 1.1-fold ACh stimulation was apparent after 7 days of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)