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 selec tive inhibitor of type 1 and 2A protein phosphatases, on the mechanica l responses evoked by oxytocin, K+- and Na+-modified solutions and oua bain in estrogen-primed rat myometrium. Oxytocin elicited a rapid, pha sic contraction followed by rhythmic oscillations. The phasic response was partially resistant to the absence of external Ca2+. Okadaic acid (1 mu M) and the L-type calcium channel blocker nifedipine (1 mu M) a bolished the oscillatory component and reduced the initial, phasic res ponse 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 ex tracellular Ca2+-dependent biphasic responses composed by an early rap id (KCl, ouabain and K+-free solution) or slower developed (25 mM Nasolution) phasic contraction followed by a sustained increase in tensi on. Okadaic acid and nifedipine, alone or in combination, abolished or decreased similarly the contractile response evoked by these stimulan ts. The okadaic acid- and nifedipine-insensitive responses to ouabain, K+-free and low Na+ solution were enhanced by increasing the extracel lular 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-sen sitive protein phosphatases play an important role in regulating myome trial contractions elicited by Ca2+ entry through voltage-sensitive Ca 2+ channels.