Marthan R, Armour C L, Johnson P R, Black J L
Department of Pharmacology, University of Sydney, N.S.W., Australia.
Respir Physiol. 1988 Feb;71(2):157-68. doi: 10.1016/0034-5687(88)90013-8.
In order to investigate the role played by extracellular calcium mobilization in activating human airway contraction, we studied the effects of A23187, a calcium ionophore, in human isolated bronchial spiral strips. In this preparation, ionophore induced a concentration dependent contraction from 10(-7) M to 10(-5) M which resulted from a direct effect on smooth muscle cells and was not a consequence of mediator release. Ionophore-induced contraction was dependent upon an entry of extracellular calcium which did not occur through the verapamil sensitive voltage dependent channel. Maximal ionophore contraction was 97 +/- 11% (n = 5) of the maximal histamine contraction but only 46 +/- 11% (n = 5) of the maximal carbachol contraction. However, when extracellular calcium concentration was doubled to 5 mM before addition of ionophore, the significant difference in amplitude between carbachol and ionophore maximal contraction was abolished. At physiological calcium concentrations addition of carbachol or histamine to the plateau of the ionophore maximal contraction produced a significant increase in the tension. Verapamil blocked the increase in ionophore tension produced only by histamine. These results suggest that (i) calcium mobilization from the extracellular source alone can produce contraction comparable in magnitude to that induced by histamine or carbachol. (ii) Extracellular calcium mobilization through different pathways has a cumulative effect on human airway contraction.
为了研究细胞外钙动员在激活人气道收缩中所起的作用，我们研究了钙离子载体A23187对人离体支气管螺旋条的影响。在此制备中，离子载体在10(-7)M至10(-5)M浓度范围内诱导浓度依赖性收缩，这是对平滑肌细胞的直接作用所致，而非介质释放的结果。离子载体诱导的收缩依赖于细胞外钙的进入，且此进入并非通过维拉帕米敏感的电压依赖性通道发生。离子载体最大收缩幅度为组胺最大收缩幅度的97±11%（n = 5），但仅为卡巴胆碱最大收缩幅度的46±11%（n = 5）。然而，在加入离子载体前将细胞外钙浓度加倍至5 mM时，卡巴胆碱与离子载体最大收缩幅度之间的显著差异消失。在生理钙浓度下，在离子载体最大收缩的平台期加入卡巴胆碱或组胺会使张力显著增加。维拉帕米仅阻断组胺所引起的离子载体张力增加。这些结果表明：（i）仅从细胞外来源动员钙就能产生与组胺或卡巴胆碱诱导的收缩幅度相当的收缩。（ii）通过不同途径进行的细胞外钙动员对人气道收缩有累积效应。
