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RESEARCH PRODUCT

Inhibitory effects of okadaic acid on rat uterine contractile responses to different spasmogens

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In the present study, we examined the effects of okadaic acid, a selective inhibitor of type I 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.