Mechanism of ouabain-induced contractions in guinea-pig tracheal rings.
The aim of the present study was to analyse the mechanism that underlies the force development induced by ouabain (ED(100) = 100 micromol/L) in guinea-pig tracheal rings. The dose-response curve showed that concentrations of ouabain above 100 micromol/L evoked smaller contractions. Ouabain, at 100 micromol/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. Both contractions induced by ouabain were dependent on extracellular Ca(2+). Consistent with this, verapamil (10 micromol/L) inhibited the first and second contractions by 77 and 59%, respectively. 3,4-Dichlorobenzamil (20 micromol/L) inhibited the first and second contractions by 68 and 97%, respectively. Simultaneous exposure to 15 mmol/L sodium solution and 100 micromol/L ouabain evoked only one transient contraction, larger (987 +/- 135 mg) than either of the ouabain-induced contractions. Inhibition of the sarcoendoplasmic reticulum Ca-ATPase with cyclopiazonic acid potentiated the first and second ouabain-induced contractions by 47 and 300%, respectively. Atropine (1 micromol/L) inhibited the first and second contractions by 44 and 76%, respectively. In conclusion, the results of the present study are relevant to the understanding of the mechanisms by which ouabain (100 micromol/L) contracts guinea-pig tracheal rings. At the muscular level, oubain induces Ca(2+) influx through L-type Ca(2+) 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 Ca(2+) influx mediated by the reverse mode of the sodium-calcium exchanger.
Espinosa-Tanguma
R
R
Departament of Fisiologia y Farmacologia, Facultad de Medicina, Universidad Autonóma de San Luis Potosí, San Luis Potosí, SLP Mexico.
Valle-Aguilera
J R
JR
Zarazúa-Garcia
O
O
Navarro-Huerta
M P
MP
Pecina
C
C
Sánchez-Armass
S
S
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology; D020746:Calcium Channels, L-Type / Q000187:drug effects; D020013:Calcium Signaling / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D012964:Sodium / Q000502:physiology; D019831:Sodium-Calcium Exchanger / Q000187:drug effects / Q000378:metabolism; D014132:Trachea / Q000187:drug effects* / Q000378:metabolism
D020746:Calcium Channels, L-Type; D002316:Cardiotonic Agents; D019831:Sodium-Calcium Exchanger; D010042:Ouabain; D012964:Sodium; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium