Mechanism of ouabain-induced contractions in guinea-pig tracheal rings.

1. The aim of the present study was to analyse the mechanism that underlies the force development induced by ouabain (ED100 = 100 µmol/L) in guinea-pig tracheal rings.2. The dose–response curve showed that concentrations of ouabain above 100 µmol/L evoked smaller contractions.3. Ouabain, at 100 µmol/L, produced two long-lasting consecutive transient contractions. The peak of the first contraction was 750 ± 75 mg, whereas the peak of the second contraction was 280 ± 46 mg.4. Both contractions induced by ouabain were dependent on extracellular Ca2+. Consistent with this, verapamil (10 µmol/L) inhibited the first and second contractions by 77 and 59%, respectively.5. 3,4-Dichlorobenzamil (20 µmol/L) inhibited the first and second contractions by 68 and 97%, respectively.6. Simultaneous exposure to 15 mmol/L sodium solution and 100 µmol/L ouabain evoked only one transient contraction, larger (987 ± 135 mg) than either of the ouabain-induced contractions.7. Inhibition of the sarcoendoplasmic reticulum Ca-ATPase with cyclopiazonic acid potentiated the first and second ouabain-induced contractions by 47 and 300%, respectively.8. Atropine (1 µmol/L) inhibited the first and second contractions by 44 and 76%, respectively.9. In conclusion, the results of the present study are relevant to the understanding of the mechanisms by which ouabain (100 µmol/L) contracts guinea-pig tracheal rings. At the muscular level, oubain induces Ca2+ influx through L-type Ca2+ channels and the reverse mode of the sodium–calcium exchanger. At the nerve terminals, ouabain promotes the release of acetylcholine secondary to the increase in Ca2+ influx mediated by the reverse mode of the sodium–calcium exchanger. [ABSTRACT FROM AUTHOR]