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Inhibitory effects of okadaic acid on rat uterine contractile responses to different spasmogens
Author(s) -
Arteche ME,
Ausina P.,
Delgado J.,
Fernandez JJ,
Norte M.,
Candenas ML,
Martín JD
Publication year - 1997
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.1997.tb00168.x
Subject(s) - okadaic acid , ouabain , endocrinology , medicine , amiloride , nifedipine , chemistry , extracellular , myometrium , phosphatase , inhibitory postsynaptic potential , calcium , oxytocin , biophysics , sodium , biochemistry , biology , uterus , enzyme , organic chemistry
Summary— 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 Ca 2+ . Okadaic acid (1 μM) and the L‐type calcium channel blocker nifedipine (1 μM) 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 Ca 2+ 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 Ca 2+ entry through voltage‐sensitive Ca 2+ channels.