血小板活化因子诱导的雪貂气管平滑肌毒蕈碱胆碱能受体超敏反应及体外腺体分泌

PAF-induced muscarinic cholinoceptor hyperresponsiveness of ferret tracheal smooth muscle and gland secretion in vitro.

作者信息

Webber S E, Morikawa T, Widdicombe J G

机构信息

Department of Physiology, St George's Hospital Medical School, London.

出版信息

Br J Pharmacol. 1992 Jan;105(1):230-7. doi: 10.1111/j.1476-5381.1992.tb14239.x.

DOI:10.1111/j.1476-5381.1992.tb14239.x

PMID:1596686

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1908609/

Abstract

The effects of exposure of the ferret trachea in vitro to platelet activating factor (PAF) were examined on methacholine-induced smooth muscle contraction, mucus volume and lysozyme outputs, and albumin transport across the tracheal epithelium. 2. Methacholine (0.1-30 microM) produced concentration-dependent increases in tracheal smooth muscle tone and mucus volume, lysozyme and albumin outputs from the trachea. 3. The concentration-response curves for methacholine-induced smooth muscle contraction, mucus volume and lysozyme outputs were all shifted upwards after exposure of the trachea to PAF (1 microM) with a significant increase in maximum response for each variable. The EC50 values for methacholine-induced smooth muscle contraction and mucus volume output were significantly reduced after PAF exposure suggesting an increase in the potency of methacholine. The concentration-response curve for methacholine-induced albumin output was shifted downwards after PAF exposure with a greatly reduced maximum but no change in the EC50 for methacholine. 4. PAF-induced hyperresponsiveness of methacholine-induced smooth muscle contraction, mucus volume and lysozyme outputs was not affected by indomethacin, FPL55712, or mepyramine and cimetidine, but was prevented by catalase and superoxide dismutase (SOD), and by WEB2086. Similarly, PAF-induced inhibition of methacholine-stimulated albumin output was prevented by catalase and SOD, and by WEB2086. 5. We conclude that PAF induces hyperresponsiveness of ferret tracheal smooth muscle and submucosal gland secretion (including lysozyme secretion from serous cells) to methacholine. This hyperresponsiveness is probably produced by receptor-mediated release of oxygen free-radicals. The inhibition of methacholine-induced albumin flux suggests a loss of epithelial function which is also probably mediated by release of free-radicals. The mechanism by which the free-radicals produce the changes in responsiveness to methacholine, and the cellular source of the free-radicals, remain to be established.

摘要

研究了雪貂气管体外暴露于血小板活化因子（PAF）对乙酰甲胆碱诱导的平滑肌收缩、黏液量和溶菌酶分泌，以及白蛋白跨气管上皮转运的影响。2. 乙酰甲胆碱（0.1 - 30微摩尔）使气管平滑肌张力、黏液量、气管溶菌酶和白蛋白分泌呈浓度依赖性增加。3. 气管暴露于PAF（1微摩尔）后，乙酰甲胆碱诱导的平滑肌收缩、黏液量和溶菌酶分泌的浓度 - 反应曲线均向上移位，每个变量的最大反应显著增加。PAF暴露后，乙酰甲胆碱诱导的平滑肌收缩和黏液量分泌的EC50值显著降低，表明乙酰甲胆碱效力增加。PAF暴露后，乙酰甲胆碱诱导的白蛋白分泌的浓度 - 反应曲线向下移位，最大反应大幅降低，但乙酰甲胆碱的EC50无变化。4. PAF诱导的乙酰甲胆碱诱导的平滑肌收缩、黏液量和溶菌酶分泌的高反应性不受吲哚美辛、FPL55712或美吡拉敏及西咪替丁的影响，但过氧化氢酶、超氧化物歧化酶（SOD）和WEB2086可阻止其发生。同样，过氧化氢酶、SOD和WEB2086可阻止PAF诱导的乙酰甲胆碱刺激的白蛋白分泌的抑制。5. 我们得出结论，PAF诱导雪貂气管平滑肌和黏膜下腺分泌（包括浆液细胞溶菌酶分泌）对乙酰甲胆碱的高反应性。这种高反应性可能是由受体介导的氧自由基释放产生的。乙酰甲胆碱诱导的白蛋白通量的抑制表明上皮功能丧失，这也可能是由自由基释放介导的。自由基产生对乙酰甲胆碱反应性变化的机制以及自由基的细胞来源仍有待确定。