Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 343, Issue 4, pp 418–426 | Cite as

Cooling-induced contraction of trachea isolated from normal and sensitized guinea-pigs

  • J. L. Ortiz
  • J. Cortijo
  • C. Sanz
  • A. De Diego
  • J. Esplugues
  • E. Morcillo


Fast (−7°C/min) cooling of guinea-pig isolated trachea produced a rapidly developing, transient contraction followed by relaxation. Cooling-induced contraction was dependent on temperature (30, 20 or 10°C) and responses in trachea obtained from actively sensitized guinea pigs were significantly greater (20 and 10°-C) than those observed in normal trachea. Cooling to 20°C was selected for subsequent experiments. Pre-treatment with sufficient concentrations of atropine, clemastine, cromoglycate, indomethacin, or nordihydroguaiaretic acid did not depress contraction to cooling in either normal or sensitized trachea. This indicates a direct effect of cooling. The contraction. produced by cooling was resistant to verapamil (1 μmol/l) or dantrolene (0.3 mmol/l). Calmodulin antagonists (trifluoperazine, W-7 and calmidazolium; all of them at 10–100 μmol/l) inhibited contraction in sensitized and normal trachea. Activators of protein kinase C (phorbol 12,13-diacetate, 1 μmol/l) enhanced while inhibitors (H-7, 20 μmol/l; staurosporine, 10 μmol/l) depressed cooling-induced contraction in both normal and sensitized tissues. Incubation (20 min) in a Ca2+ -free solution inhibited cooling-induced contraction in normal but not in sensitized trachea. Exposure to a low Na+ (25 mmol/l) or a K+-free medium abolished contraction to cooling in normal and sensitized trachea. Ouabain (0.1–10 μmol/l) and vanadate (0.01–5 mmol/l) inhibited cooling-induced-contraction to a greater extent in normal than in sensitized trachea. Polymyxin B (0.5 mmol/l) selectively depressed responses to cooling in sensitized trachea. In a separate series of experiments, it was shown that sensitized trachea was hyperresponsive to ouabain and vanadate. Previous cooling to 20°C abolished responses to ouabain but only attenuated those to vanadate. These results are compatible with an enhancement of Na+,K+-ATPase and Ca2+-ATPase activities in sensitized trachea and further support the notion that intracellularly stored Ca2+ plays a decisive role in the activation of sensitized tracheal muscle.

Key words

Airway smooth muscle Guinea-pig trachea Cooling Ouabain Vanadate 


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Copyright information

© Springer-Verlag 1991

Authors and Affiliations

  • J. L. Ortiz
    • 1
  • J. Cortijo
    • 1
  • C. Sanz
    • 1
  • A. De Diego
    • 1
  • J. Esplugues
    • 1
  • E. Morcillo
    • 2
  1. 1.Department of Pharmacology, Faculty of MedicineUniversity of ValenciaMadridSpain
  2. 2.Department of Pharmacology, Faculty of MedicineUniversity of Alcalá de HenaresMadridSpain

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