Inhibitory effects of okadaic acid on rat uterine contractile responses to different spasmogens.
In the present study, we examined the effects of okadaic acid, a selective inhibitor of type 1 and 2A protein phosphatases, on the mechanical responses evoked by oxytocin, K(+)- and Na(+)-modified solutions and ouabain in estrogen-primed rat myometrium. Oxytocin elicited a rapid, phasic contraction followed by rhythmic oscillations. The phasic response was partially resistant to the absence of external Ca2+. Okadaic acid (1 microM) and the L-type calcium channel blocker nifedipine (1 microM) abolished the oscillatory component and reduced the initial, phasic response to about 80% of the control response. High K+ (60 mM) solution, ouabain (1 mM), K(+)-free medium and low Na+ (25 mM) solution induced extracellular Ca(2+)-dependent biphasic responses composed by an early rapid (KCl, ouabain and K(+)-free solution) or slower developed (25 mM Na+ solution) phasic contraction followed by a sustained increase in tension. Okadaic acid and nifedipine, alone or in combination, abolished or decreased similarly the contractile response evoked by these stimulants. The okadaic acid- and nifedipine-insensitive responses to ouabain, K(+)-free and low Na+ solution were enhanced by increasing the extracellular concentration of Ca2+ in the medium and were inhibited in a dose-dependent manner by amiloride (0.05-0.5 mM). These data suggest that, in estrogen-primed rat uterus, dephosphorylating mechanisms by OA-sensitive protein phosphatases play an important role in regulating myometrial contractions elicited by Ca2+ entry through voltage-sensitive Ca2+ channels.
Arteche
M E
ME
Departmento de Farmacología, Facultat de Farmàcia, Universitat de València, Spain.
Ausina
P
P
Delgado
J
J
Fernández
J J
JJ
Norte
M
M
Candenas
M L
ML
Martín
J D
JD
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D009543:Nifedipine / Q000494:pharmacology*; D019319:Okadaic Acid / Q000494:pharmacology*; D010042:Ouabain / Q000494:pharmacology; D010121:Oxytocin / Q000494:pharmacology; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors*; D011188:Potassium / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000494:pharmacology; D014590:Uterine Contraction / Q000187:drug effects* / Q000502:physiology
D002121:Calcium Channel Blockers; D019319:Okadaic Acid; D010121:Oxytocin; D010042:Ouabain; D012964:Sodium; D010744:Phosphoric Monoester Hydrolases; D009543:Nifedipine; D011188:Potassium; D002118:Calcium