The effects of progesterone, prostaglandin F2alpha and oxytocin on the calcium-activation of the uterus.
The relationship between "activator-calcium" (A-Ca), progesterone (P), prostaglandin F2alpha (PGF2alpha) and oxytocin (Oxy) has been examined in 100 uterine strips of 34 pregnant and 100 strips of 34 post partum rabbits. At the 25th day of gestation, uterine P was 13.9+/-1.3 ng/g, while within 3-12 hours post partum 3.3+/-0.3 ng/g tissue (P less than 0.001). Uterine strips, mounted isometrically in Krebs' solution, sustained maximum excitability in a steady state when exposed every 30 seconds for 4 seconds to an electric field of 12 V/5 cm (a.c.). The maximally contracting muscles were then rinsed at intervals of 6 minutes with Ca-free Krebs. In Ca-free Krebs, the post partum uterus lost 31% of its Ca and 96% of its excitability in a short 25 minutes, while the pregnant uterus lost 30% of its Ca and 93% of its excitability in 50 minutes (P less than 0.001). Since the extracellular space is approximately 30% in the uterus, this approximately 30% Ca, lost by both muscles, most probably was extracellular Ca and the small A-Ca fraction which is presumably "bound" more strongly at the membrane systems of the P-dominated pregnant, than the non-dominated post partum uterus. The significantly faster and more complete recovery from Ca-deficiency and inexcitability of the pregnant than the post partum uterus (P less than 0.001), at different levels of external Ca, further substantiates this premise. So does the demonstration that exposure to Ca-free Krebs increases 45Ca-efflux 400% in the post partum and only 110% in the pregnant uterus (P less than 0.001). Exposure to 100 ng/ml PGF2alpha in normal Krebs has a similar effect on the 45Ca-efflux of the post partum uterus, while the response of the pregnant uterus is indistinct (P less than 0.001). These highly significant differences between the post partum and the pregnant uteri in their Ca-efflux explain the higher threshold (P less than 0.001) and lower "sensitivity" to PGF2alpha and Oxy (P less than 0.001) of the pregnant than the post partum uterus. The already very highly significant differences between the two muscles, in threshold and sensitivity to these two most potent oxytocics, were increased still further by rendering the uterine strips Ca-deficient. All together, these findings substantiate the early contention (1-7, 18, 19) that uterine function at the cellular level is regulated by opposing actions of the suppressor P and the intrinsic stimulant PG or other oxytocic agents on threshold, excitability and the Ca-activation of the contractile process.
D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D010121:Oxytocin / Q000494:pharmacology*; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology*; D011460:Prostaglandins F / Q000494:pharmacology*; D011817:Rabbits; D013268:Stimulation, Chemical; D013997:Time Factors; D014590:Uterine Contraction / Q000187:drug effects*; D014599:Uterus / Q000378:metabolism*
D011460:Prostaglandins F; D011374:Progesterone; D010121:Oxytocin; D002118:Calcium