The effect of prostaglandin F2 α on the activator calcium of the uterus

Abstract

The mechanism through which PGF2 α exerts its oxytocic action was studied in 150 uterine strips, 48 excised from 25 days pregnant and 102 from post partum rabbits. PGF2 α 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 CaCl 2 was replaced in the KRB. This effect of PGF2 α 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 PGF2 α but only during stimulation with 12 V/5 cm and not with 60 V/5 cm. This finding suggests that while the effect of PGF2 α 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 CaCl 2, PGF2 α restored excitability slowly, indicating that PGF2 α 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 PGF2 α did not promote 45Ca-efflux when 40Ca-influx was inhibited by Verapamil. This demonstration provided more direct evidence that PGF2 α promotes the influx of the A-Ca and thus explained the mechanism of action of this key regulator at the molecular level.