Cooling-induced bronchoconstriction: The role of ion-pumps and ion-carriersystems

The mechanism of cold-induced bronchoconstriction is poorly understood. Our previous results show that cooling-induced contractions (CIC) do not invol ve activation of cell surface receptor systems nor innervation nor Ca2+ upt ake. However, the results show that CIC is mainly dependent on intracellula r Ca2+ [32]. Isolated tracheal strips and bronchiolar segments were suspend ed in organ baths containing Krebs' solution for isometric tension recordin g. Tissue responses during stepwise cooling from 37 to 5 degrees C were exa mined. Cooling ovine tracheal strips and bronchiolar ring segments to 20 de grees C caused a rapid contraction which decreased slowly until it reached the basal level in approximately 30 min. There is a significant inhibition of Ca-45(2+) efflux at 20 degrees C to those incubated at 37 degrees C. Thi s prompted this study whose aim was to determine the role of ion-pump and i on-carrier systems on cooling mechanisms. Inhibition of the Na+/K+ pump wit h ouabain (10 mu M) evoked contraction in tracheal and bronchiolar preparat ions. When cooling was superimposed on this contraction the cooling-induced contractions were reduced in the bronchiolar segments. In the tracheal str ips, at temperatures down to 15 degrees C ouabain converted the contraction s to a relaxation, but further cooling to 10 and 5 degrees C resulted in co ntractions that were similar to control at 5 degrees C. Staurosporine, a pr otein kinase inhibitor (1 mu M) enhanced CIC in trachea and bronchiole. Van adate, a Ca2+-ATPase pump inhibitor (1 mM) potentiated CIC in the two prepa rations. Trifluoperazine and W-7, calmodulin antagonists (10 and 100 mu M) enhanced CIC in tracheal preparations but not in the bronchiolar segments. Thapsigargin and cyclopiazonic acid (CPA), inhibitors of sarcoplasmic retic ulum (SR) Ca2+-ATPase pump (1 and 10 mu M) potentiated CIC in tracheal but not in bronchiolar preparations. Amiloride, Na+/H+ and Na+/Ca2+ exchange sy stem inhibitor (1 mM) abolished CIC in both trachea and bronchiole. These r esults show a strong relationship between cooling and the activity of ion t ransport systems and indicate that CIC is due to inhibition of calcium remo val mechanisms as a result of inhibition of these ion-pump and ion carrier systems. (C) 1999 The Italian Pharmacological Society.