COOLING-INDUCED BRONCHOCONSTRICTION: THE ROLE OF ION-PUMPS AND ION-CARRIER SYSTEMS

Abstract

The mechanism of cold-induced bronchoconstriction is poorly understood. Our previous results show that cooling-induced contractions (CIC) do not involve activation of cell surface receptor systems nor innervation nor Ca2+uptake. However, the results show that CIC is mainly dependent on intracellular Ca2+[32]. Isolated tracheal strips and bronchiolar segments were suspended in organ baths containing Krebs' solution for isometric tension recording. Tissue responses during stepwise cooling from 37 to 5°C were examined. Cooling ovine tracheal strips and bronchiolar ring segments to 20°C caused a rapid contraction which decreased slowly until it reached the basal level in approximately 30 min. There is a significant inhibition of45Ca2+efflux at 20°C to those incubated at 37°C. This prompted this study whose aim was to determine the role of ion-pump and ion-carrier systems on cooling mechanisms. Inhibition of the Na+/K+pump with ouabain (10 μm) evoked contraction in tracheal and bronchiolar preparations. When cooling was superimposed on this contraction the cooling-induced contractions were reduced in the bronchiolar segments. In the tracheal strips, at temperatures down to 15°C ouabain converted the contractions to a relaxation, but further cooling to 10 and 5°C resulted in contractions that were similar to control at 5°C. Staurosporine, a protein kinase inhibitor (1 μm) enhanced CIC in trachea and bronchiole. Vanadate, a Ca2+-ATPase pump inhibitor (1 mm) potentiated CIC in the two preparations. Trifluoperazine and W-7, calmodulin antagonists (10 and 100 μm) enhanced CIC in tracheal preparations but not in the bronchiolar segments. Thapsigargin and cyclopiazonic acid (CPA), inhibitors of sarcoplasmic reticulum (SR) Ca2+-ATPase pump (1 and 10 μm) potentiated CIC in tracheal but not in bronchiolar preparations. Amiloride, Na+/H+and Na+/Ca2+exchange system inhibitor (1 mm) abolished CIC in both trachea and bronchiole. These results show a strong relationship between cooling and the activity of ion transport systems and indicate that CIC is due to inhibition of calcium removal mechanisms as a result of inhibition of these ion-pump and ion carrier systems.