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.
Calcimycin Calcium