Methacholine sensitivity and cAMP protein kinase in tracheal smooth muscle.
Methacholine sensitivity and cAMP protein kinase in tracheal smooth muscle.
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气管平滑肌乙酰甲胆碱敏感性和 cAMP 蛋白激酶。
DOI：
10.1152/jappl.1986.60.3.1043
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发表时间：
1986
期刊：
影响因子：
--
通讯作者：
Mayer,SE
中科院分区：
文献类型：
--
作者：
Jensen,AD;Puckett,AM;Rinard,GA;Torphy,TJ;Mayer,SE
我们研究了犬气管平滑肌敏感性和对乙酰甲胆碱的反应性的区域差异，以及基础和乙酰甲胆碱刺激的腺苷 3',5'-环单磷酸 (cAMP) 和 cAMP 依赖性蛋白激酶活性。环状软骨和隆突之间的气管被分为三个等长的部分（指定为颈部、中部和胸部区域），每个部分由大约 12-14 个软骨环组成。将三个区域中每个区域的平滑肌条暴露于累积半对数增量的氯化乙酰甲胆碱。根据这些数据确定每个区域中平滑肌对醋甲胆碱的敏感性（-log EC50）和响应性（每横截面积的力和每毫克蛋白质的力）。将来自颈部和胸部区域的平滑肌条在暴露于累积半对数增量乙酰甲胆碱之前和之后冷冻，直至每个区域先前确定的EC50。测定冷冻样品的 cAMP 含量或 cAMP 依赖性蛋白激酶活性。研究了静息张力与乙酰甲胆碱敏感性和反应性之间的关系。对于我们使用的尺寸条带，4 g 静息张力将平均颈部和胸部条带分别设置为其最佳长度的 96% 和 101%。乙酰甲胆碱 EC50 不受静息张力变化的影响。颈部、中部和胸部区域对乙酰甲胆碱的敏感性分别为 7.1、6.8 和 6.5。在 EC50 乙酰甲胆碱下，颈部和胸部平滑肌对乙酰甲胆碱的反应性分别为 16.4 和 16.3 g 力/mm2。颈部平滑肌的基础cAMP 低于胸部。在基础和 EC50 乙酰甲胆碱刺激条件下，颈部平滑肌中的 cAMP 依赖性蛋白激酶活性比均低于胸部平滑肌。我们在气管平滑肌中观察到乙酰甲胆碱敏感性与 cAMP 或 cAMP 依赖性蛋白激酶活性之间存在反比关系。我们认为 cAMP 和 cAMP 依赖性蛋白激酶在气道平滑肌对胆碱能激动剂敏感性的调节中发挥作用。
We studied regional variation in canine trachealis smooth muscle sensitivity and responsiveness to methacholine as well as basal and methacholine-stimulated adenosine 3′,5′-cyclic monophosphate (cAMP) and cAMP-dependent protein kinase activity. The trachea between the cricoid cartilage and the carina was divided into three segments of equal length (designated cervical, middle, and thoracic regions), each consisting of approximately 12–14 cartilage rings. Smooth muscle strips from each of the three regions were exposed to cumulative half-log increments of methacholine chloride. The sensitivity (-log EC50) and responsiveness (force per cross-sectional area and force per milligram protein) of the smooth muscle to methacholine in each region was determined from these data. Smooth muscle strips from cervical and thoracic regions were frozen before and after exposure to cumulative half-log increments of methacholine up to each region's previously determined EC50. Frozen samples were assayed for cAMP content or cAMP-dependent protein kinase activity. The relationship between resting tension and methacholine sensitivity and responsiveness were studied. For the size strips we used, 4 g resting tension set the average cervical and thoracic strips at 96 and 101% of their optimal length, respectively. The methacholine EC50 was not affected by a variation in resting tension. Sensitivity to methacholine was 7.1, 6.8, and 6.5 for cervical, middle, and thoracic regions, respectively. The responsiveness of the cervical and thoracic smooth muscle to methacholine was 16.4 and 16.3 g force/mm2, respectively, at an EC50 methacholine. Basal cAMP was lower in cervical smooth muscle than in thoracic. cAMP-dependent protein kinase activity ratios under both basal and EC50 methacholine-stimulated conditions were lower in cervical smooth muscle than in thoracic. We have observed in trachealis smooth muscle an inverse relationship between methacholine sensitivity and either cAMP or cAMP-dependent protein kinase activity. We suggest that cAMP and cAMP-dependent protein kinase play a role in the regulation of airway smooth muscle sensitivity to cholinergic agonists.