1. Pharmacological modulation of the spasmogenic response to methylxanthines in guinea-pig trachea.
- Author
-
Cortijo J, Sanz CM, Villagrasa V, Anton M, and Morcillo EJ
- Subjects
- Animals, Caffeine antagonists & inhibitors, Caffeine pharmacology, Calcium metabolism, Electric Stimulation, Female, Guinea Pigs, In Vitro Techniques, Indomethacin pharmacology, Isometric Contraction drug effects, Male, Muscle Contraction drug effects, Protein Kinase C antagonists & inhibitors, Sodium metabolism, Theophylline antagonists & inhibitors, Theophylline pharmacology, Trachea drug effects, Xanthines antagonists & inhibitors, Muscle, Smooth drug effects, Parasympathomimetics pharmacology, Xanthines pharmacology
- Abstract
The spasmogenic activity of methylxanthines was evaluated in guinea-pig isolated trachea treated with indomethacin (2.8 microM) and cooled to 20 degrees C. The contraction elicited by caffeine or theophylline (10 mM) was reduced in the presence of ouabain (10 microM), amiloride (100 microM), staurosporine (1 microM), H-7 (50 microM), polymyxin B (500 microM), K(+)-free solution, low Na+ (25 mM) medium or Ca(2+)-free (EGTA 0.1 mM) solution but was unaltered in the presence of verapamil (10 microM) or vanadate (10-100 microM). These results suggest that tracheal spasm to methylxanthines predominantly involves Ca2+ release from intracellular stores with a minor component due to extracellular Ca2+ entry through verapamil-insensitive pathways. A Na+/Ca2+ exchange process and the activation of protein kinase C may be also involved. more...
- Published
- 1993