Effects of dantrolene on the responses to methylxanthines in the isolated guinea-pig trachea

The effect of dantrolene on the responses to methylxanthines (caffeine and theophylline) and a β-adrenoceptor agonist (salbutamol) was studied in isolated guinea-pig trachea. Caffeine and theophylline (1 μM-10 mM) and salbutamol (1 nM-10 μM) produced concentration-dependent relaxation of spontaneous and stimulated (acetylcholine 1 mM) tone. Responses to high concentrations (10 mM) of caffeine and theophylline added to tracheal strips either unstimulated (spontaneous tone) or indomethacin (2.8 μM)-treated were reversed to contractions in the presence of dantrolene (3 μM-0.3 mM). This effect was not observed for salbutamol or when relaxant responses to the agonists were generated in pre-contracted (acetylcholine 1 mM) strips. Dantrolene inhibited concentration dependently the contraction evoked by caffeine (1 mM) in indomethacin (2.8 μM)-treated strips at 20 °C. This effect of dantrolene was attenuated in a low Ca 2+ (0.8 mM) medium or when the bath temperature was lowered to 10 °C. Although an intracellular site of action cannot be excluded these results suggest that dantrolene mainly interferes with transmembrane Ca 2+ movements in the guinea-pig trachea.