The effect of prostaglandin F2α on the activator calcium of the uterus

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 CaCl₂ 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 CaCl₂, 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.     

The effect of prostaglandin F2 alpha on third stage labor.

The effects of intramyometrially injected PGF2 alpha intravenous Ergometrin and no treatment were compared during 3rd stage labor in 140 patients. In comparison with Ergometrin or no treatment, PGF2 alpha significantly reduced the duration of 3rd stage labor, blood loss, incidence of subinvolution and subfebrility.     

Histophysiological studies of prostaglandin F2alpha on isolated organs. I. Effect of prostaglandin F2alpha on the heart.

The physiological and histochemical effects of PGF2alpha on isolated rabbit hearts were examined. The results showed a positive inotropic effect. The coronary flow increased. From the histochemical studies, adenosine triphosphatase (ATP-ase) and succinic dehydrogenase activities were increased while that of alkaline phosphatase was decreased. Glycogen granules were depleted. These findings were discussed on a histophysiological basis.     

Absence of uterokinetic effects of prostaglandin F 2 alpha on oxytocin-reactive uterus in the mare

In most cyclic females, prostaglandin F(2alpha) (PGF(2alpha)) triggers a uterine motility response resembling that of oxytocin (OT). To determine if PGF(2alpha) is a uterokinetic substance in the cycling mare, uterine motility was measured by intrauterine balloon technique in 12 conscious, normally cyclic mares. After 60 min of saline infusion, continuous intravenous (i.v.) infusion with OT (1 i.u./min) was followed by PGF(2alpha) (200 mug/min) for 60 min each. The experiment was repeated 3 wk later except with PGF(2alpha) preceeding OT. A second group of mares was administered OT (60 i.u.) either i.v., intramuscularly (i.m.), or intrauterinely (i.u.). Plasma samples were studied for progesterone concentration. Control uterine motility for the first group of mares was (mean +/- SEM) 545.83 +/- 45.10 mm(2). Significant (P<0.05) elevation in uterine motility was recorded for OT (1118.60 +/- 70.56 mm(2)) regardless if PGF(2alpha) preceded OT infusion or vice-versa. No significant difference (P>0.05) was seen in motility after PGF(2alpha) (423.33 +/- 31.12 mm(2)) infusion. The uterokinetic effect of OT was greatest when OT was administered i.v. (1696.50 +/- 195.46 mm(2)) followed by i.m. (819.82 +/- 39.96 mm(2)), and it was least effective when administered i.u. (607.83 +/- 21.56 mm(2)) as compared to control uterine motility (279.78 +/- 22.33 mm(2)). Skin electrical resistance values rose from 0 to 2000 ohms with PGF(2alpha) infusion (but not with OT), indicating that PGF(2alpha) was bioactive. It was concluded that PGF(2alpha) was not a uterokinetic substance in the cyclic mare.     

The effects on stretching and prostaglandin F2alpha on the contractile and bioelectric activity of the uterus in rat.

The effects of stretching and of prostaglandin F2alpha on spontaneous and induced with local deformation contractile activity of rat uterus were studied. It was found that stretching the uterus up to the length of the decontracted organ in vivo increased the contractile and bioelectric activity. The rise in spontaneous uterine activity was a factor reducing induction of additional contractions. The fall in the level of endogenous prostaglandins in the uterus following administration of indomethacin inhibited the spontaneous contractile activity but was without effect on the contractions induced by local deformation of the myometrium. Prostaglandin F2alpha added to the bath in a concentration of 0.001 ng/ml exerted an inhibitory action on the different tested parameters of the contractile activity. After high doses stimulation of the uterine activity was observed.     

The effect of prostaglandin F2 alpha administration on progesterone after hysterectomy of guinea-pigs

It is believed that in guinea-pigs the main luteolytic agent is prostaglandin F2 alpha (PGF2a) and that it is synthesised in the uterus. In this study non-pregnant guinea-pigs were hysterectomised at Day 5 of the estrous cycle. Peripheral progesterone levels in animals from which the uterus had been removed remained elevated for an extended time. The results suggested the corpora lutea (CL) had an inherent life span in excess of the length of the estrous cycle. However after a time the levels of circulating progesterone declined, suggesting there might have been a reduction of a stimulating factor or the appearance of a non-uterine luteolysin. If after hysterectomy PGF2a was administered 4 and 5 days later then there was a reduction in the mean progesterone level but the decline did not continue. The CL at the stage of the experimental procedure were sensitive to luteolysin but they had retained their capability to resist endocrinological insult. The study provided further support for the contention that control of PGF2a activity is vital for progesterone maintenance. Additionally, the cells of the CL have the potential to be the site of some of the PGF2a control.     

The effect of prostaglandin F2 alpha administration on progesterone after hysterectomy of guinea-pigs

It is believed that in guinea-pigs the main luteolytic agent is prostaglandin F2 alpha (PGF2a)_and that it is synthesised in the uterus. In this study non-pregnant guinea-pigs were hysterectomised at Day 5 of the estrous cycle. Peripheral progesterone levels in animals from which the uterus had been removed remained elevated for an extended time. The results suggested the corpora lutea (CL) had an inherent life span in excess of the length of the estrous cycle. However after a time the levels of circulating progesterone declined, suggesting there might have been a reduction of a stimulating factor or the appearance of a non-uterine luteolysin. If after hysterectomy PGF2a was administered 4 and 5 days later then there was a reduction in the mean progesterone level but the decline did not continue. The CL at the stage of the experimental procedure were sensitive to luteolysin but they had retained their capability to resist endocrinological insult. The study provided further support for the contention that control of PGF2a activity is vital for progesterone maintenance. Additionally, the cells of the CL have the potential to be the site of some of the PGF2a control.     

Role of prostaglandin F2alpha in ovulation.

Using radioimmunoassay procedures, the levels of plasma, uterine and ovarian prostaglandin (PG) F2alpha, and those of plasma estradiol and progesterone were measured in intact, hysterectomized or ovariectomized immature female rats pretreated with PMS and subsequent HCG. Occurrence of ovulation was confirmed at 8 hours after the HCG administration not only in the intact rats but also in the hysterectomzied rats. The levels of plasma estradiol and progesterone, and of uterine and ovarian PGF2alpha rose with the PMS injection alone, but they did not reach the peaks before the HCG administration. Both plasma estradiol and uterine PGF2alpha showed a peak at 2 hours after the HCG injection. These peaks were antecedent 2 or 6 hours before the peaks of ovarian and plasma PGF2alpha, respectively. However, such increase of uterine PGF2alpha does not seem to be indispensable for ovulation, because ovulation could occur in the hysterectomized rats. The levels of ovarian PGF2alpha showed a high plateau from 4 to 8 hours after the HCG injection, and then rapidly decreased after ovulation. The levels of plasma PGF2alpha peaked not only in the intact rats but also in the hysterectomized rats at 8 hours after the HCG treatment. But in the ovariectomized rats, this plasma PGF2alpha peak at 8 hours disappeared and there was no statistical change of plasma PGF2alpha throughout the PMS-HCG treatment. Plasma progesterone gradually increased and reached the maximum at 10 hours after the HCG injection. These results conclude that the main source of increased plasma PGF2alpha during the ovulatory process induced with the PMS-HCG treatment is the ovary, and it is strongly suggested that a rapid increase of PGF2alpha in the ovary may play some important role(s) in the ovulatory process.     

The effect of the prostaglandin F2alpha analogue ICI 81008 on uterine small arteries and on blood pressure.

The effects of PGF2alpha and its analogue ICI 81008 have been compared on the small arteries of the omentum uteri on the rat. The vessels measured 20-80 mum in diameter and were examined by intra-vital-microscopy. While the maximum responses of PGF2alpha and ICI 81008 were similar, the duration of the effect of ICI 81008 was significantly longer (P is less than 0.001). At 15 minutes after the administration of the drugs the effect of ICI 81008 was still almost maximal, while the PGF2alpha response disappeared.     

Effect of prostaglandin F2 alpha on the neurohypophysis. A histochemical study.

Ten micrograms of PG F2 alpha in distilled water were injected intraperitoneally into thirty non-pregnant female rats and their hypophysis was studied after aldehyde-fuchsin and performic acid-alcian blue staining. A definite depletion of posterior pituitary principle was observed in the hypophysis. The role of oxytocin in relation to the oxytocic effect of prostaglandin F2 alpha is discussed.