Abstract: | The mechanism through which PGF2α exerts its oxytocic action was studied in 150 uterine strips, 48 excised from 25 days pregnant and 102 from post partum rabbits. PGF2α delayed the loss of excitability upon exposure of the uterus to Ca-free Krebs Ringer Bicarbonate (KRB) solution and accelerated recovery when half (1.25 mM) of the normal CaCl2 was replaced in the KRB. This effect of PGF2α was more pronounced in the post partum than the pregnant uterus, which resisted Ca-deficiency by high affinity binding in its plasma membrane of the activator-Ca (A-Ca).The Ca-ionophore A23187 simulated the action of PGF2α but only during stimulation with 12 V/5 cm and not with 60 V/5 cm. This finding suggests that while the effect of PGF2α is limited to a control of the movement of the extracellular and membrane-bound Ca, A23187 affects the distribution of Ca liberated by the strong (60 V/5 cm) electric field from internal stores of the myometrial cells. In the presence of Ruthenium-red (a Ca-influx inhibitor) and only 1.25 mM CaCl2, PGF2α restored excitability slowly, indicating that PGF2α is an oxytocic agent because it promotes Ca-influx. However, knowing that Ca-efflux is in part dependent upon Ca-influx the most informative present finding was the observation that PGF2α did not promote 45Ca-efflux when 40Ca-influx was inhibited by Verapamil. This demonstration provided more direct evidence that PGF2α promotes the influx of the A-Ca and thus explained the mechanism of action of this key regulator at the molecular level. |