Release Of Prostaglandin F2 Alpha Research Articles

Protein synthesis and degradation in isolated muscle. Effect of omega 3 and omega 6 fatty acids.

The ability of derivatives of the essential fatty acids linoleic acid (C18:2, omega 6) and alpha-linolenic acid (C18:3, omega 3) to stimulate rates of protein synthesis and degradation was investigated in isolated intact muscles from fasted rabbits. Both omega 6 derivatives examined, arachidonic acid (C20:4, omega 6) and dihomo-gamma-linolenic acid (C20:3, omega 6), when added at concentrations up to 1 microM, stimulated the rate of protein synthesis and the release of prostaglandin F2 alpha (PGF2 alpha). Metabolites of the omega 6 series, namely eicosapentaenoic acid (C20:5, omega 3) and docosahexaenoic acid (C22:6, omega 3), were without effect on the rate of protein synthesis and resulted in a decrease in the release of PGF2 alpha. None of the fatty acids had a significant effect on the rate of protein degradation. Although insulin (100 mu units/ml) also stimulated rates of protein synthesis when added alone, none of the omega 3 or omega 6 fatty acids, when added with insulin at concentrations of 0.2 microM, potentiated the effect of the hormone.

The role of ovine conceptus secretory proteins in the establishment of pregnancy.

Sheep (Ovis aries) that are not pregnant have recurring estrous cycles of about 17 days’ duration during the breeding season, i.e., August through December to January. The first day of behavioral estrus is designated Day 0 with ovulation occurring about 30h after onset of estrus and the ovulatory surge of Luteinizing Hormone (LH). The estrous cycle is characterized by growth (Days 4–12) and then regression (luteolysis) of the corpus luteum (CL). Luteolysis begins on about Day 15 after onset of estrus. Prostaglandin F2-alpha (PGF), produced by the uterine endometrium, is the uterine luteolytic hormone in sheep (1). Beginning on Days 14 to 15 and continuing until the onset of the next period of estrus, PGF is released in a pulsatile manner. About 5 episodes of PGF release per 24h are required for luteolysis (2,3).KeywordsCorpus LuteumEstrous CycleUterine HornOxytocin ReceptorUterine EndometriumThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Effect of pregnancy on oxytocin-induced release of prostaglandin F2 alpha in heifers.

The effect of pregnancy on the release of prostaglandin F2 alpha (PGF2 alpha) in response to oxytocin (OT) has been examined. Fourteen cyclic heifers received one intravenous injection of 1 IU OT (n = 6) or 100 IU OT (n = 8) 17, 18, or 19 days (Day 17-19) after the onset of estrus (Day 0). Five of these animals also received 100 IU OT at Days 6 and 13 to determine the effect of OT at different times of the cycle. Frequent blood samples were taken for 60 min before and for 90 min after OT injection for the measurement of 15-keto-13,14-dihydro-PGF2 alpha (PGFM) by radioimmunoassay. The experiment was then repeated using the same animals at Day 17-19 of pregnancy (confirmed by the recovery of an embryo the day after OT injection). Following the injection of 1 IU OT, plasma PGFM reached its peak within 30 min with the increase significantly lower (P less than 0.05) in pregnant (1.13 +/- 0.10-fold) than in nonpregnant animals (2.07 +/- 0.27-fold). However, because only 3 of the 6 cyclic animals showed a response to 1 IU OT, the dose was increased to 100 IU in subsequent experiments. The animals that received 100 IU at Days 6 and 13 had no significant increase in PGFM concentrations (1.18 +/- 0.05-fold and 1.01 +/- 0.04-fold, respectively). At Day 17-19 the increase in plasma PGFM reached its peak 5-15 min after 100 IU OT and the increase was significantly greater in nonpregnant (3.23 +/- 0.17-fold) than in pregnant (1.21 +/- 0.02-fold; P = 0.003) heifers. Six of 11 animals injected at Day 17-19 of the cycle showed a decrease in progesterone (P4) the day after OT administration. These data show that the release of PGF2 alpha in response to OT is suppressed in pregnant animals in vivo, suggesting an antiluteolytic role for the embryo in luteostasis.

Role of cyclooxygenase products in the lung action of leukotrienes A4, B4, C4, D4 and E4.

Leukotrienes (LT) LTA4, LTB4, LTC4, LTD4 and LTE4 induced marked contractions of guinea pig lung parenchymal strips mounted in organ baths. These contractions were inhibited differentially (40-50% for LTA4, LTC4, LTD4 and LTE4, and 90% for LTB4) by indomethacin (20 micrograms.ml-1; 55.9 microM). Two novel inhibitors of thromboxane synthetase (OKY-1581 and OKY-046) reduced the myotropic activity of the lung strips and the release of prostaglandins and thromboxanes from the perfused guinea pig lungs stimulated by LTB4 and LTD4. The release of cyclooxygenase products prostaglandin F2 alpha, thromboxane B2 and 12-hydroxyheptadecatrienoic acid by guinea pig lungs following stimulation with LTB4 and LTD4 was also measured by gas chromatography-mass spectrometry. The role of prostaglandins and thromboxanes in the lung actions of leukotrienes was confirmed using a cascade superfusion system and classical organ baths. Although prostaglandins and thromboxanes contribute to the contractile effect of LTB4 on the guinea pig lung whereas they may play a lesser role in the action of the peptidoleukotrienes (approx. 40-50%), stimulation of their release by the peptidoleukotrienes is many times more effective than by LTB4.

Endometrial and myometrial prostaglandin release during the menstrual cycle in relation to menstrual blood loss.

Endometria and myometria were collected at hysterectomy from 42 women with measured menstrual blood loss. Specimens were obtained throughout the menstrual cycle [menstrual (n = 11), follicular (n = 9), early luteal (n = 6), midluteal (n = 9), and late luteal (n = 7)]. In vitro endometrial and myometrial release of prostaglandin F2 alpha (PGF2 alpha), PGE2, and 6-keto-PGF1 alpha were examined using a superfusion technique. In the endometrium, the principal PG produced was PGF2 alpha, while in the myometrium, it was 6-keto-PGF1 alpha. Cyclical changes in PG release were found only in the endometrium, with an increase toward the end of the menstrual cycle and during menstruation. No significant correlation was found between menstrual blood loss (range, 4-840 ml) and PGF2 alpha, PGE2, or 6-keto-PGF1 alpha release in either endometrium or myometrium. Furthermore, there was no correlation between either the PGF2 alpha to PGE2 or the PGF2 alpha to 6-keto-PGF1 alpha ratios and menstrual blood loss.

The influence of changes in tension on protein synthesis and prostaglandin release in isolated rabbit muscles.

Intermittent stretching of isolated rabbit muscles increased the rate of protein synthesis by 70% and prostaglandin-F2 alpha release by 105%. Both effects of intermittent stretching were blocked by indomethacin and meclofenamate; the absence of Ca2+ together with added EGTA also inhibited both processes. The residual influence of intermittent stretching on protein synthesis was closely correlated with prostaglandin-F2 alpha release, which may be the link between mechanical activity and protein synthesis in skeletal muscle.

Oxytocin induces maternal behavior in virgin female rats.

Intracerebroventricular administration of oxytocin to virgin female rats that had been ovariectomized and primed with estrogen 48 hours previously induced a rapid onset of full maternal behavior. The maternal behavior persisted and its incidence was dose-related. Tocinoic acid, the ring structure of oxytocin, also rapidly induced the onset of persistent, full maternal behavior. Arginine vasopressin induced persistent maternal behavior, but this behavior had a later onset. Prostaglandin F2 alpha induced strong partial maternal behavior, which showed early onset but did not persist. Many other peptides, ovarian steroids, and prostaglandin E2 were no more effective than saline. These findings suggest that the release of oxytocin and prostaglandin F2 alpha during labor may promote maternal behavior in rats.

Thromboxane B2, 6-keto-prostaglandin F1 alpha, and prostaglandin F2 alpha production by contracting pregnant rate uteri in vitro.

While prostaglandin production by uterine tissue has been shown to be involved in the contractile mechanism of this tissue, less attention has focused upon the involvement of other prostanoids. We have simultaneously measured in vitro isometric contractility of pregnant rat uteri with the release of prostaglandin F2 alpha (PGF), 6-keto-prostaglandin F1 alpha (6-k-PGF1 alpha) and thromboxane B2 (TXB2) into the bathing medium under various conditions. Frequency of uterine contractions and integrated contractile force (ICF) increased from 15 days of gestation and peaked at the time of parturition. Activity was generally greatest during the first 15 min of incubation except during parturition and on Day 1 postpartum when the uterine segment remained active for 1 h experimental period. Indomethacin (INDO) significantly reduced contractile activity regardless of gestational stage. PGF, TXB2, and 6-k-PGF1 alpha increased with gestational age, peaking at the time of parturition. Production was greatest during the first 15 min of incubation and INDO inhibited production of each prostanoid regardless of gestational stage. Imidazole (100 micrograms/ml) inhibited TXB2 production without affecting PGF or 6-k-PGF1 alpha levels. Frequency of contraction and ICF were not affected by imidazole treatment despite TXB2 reduction. These data demonstrate that the in vitro uterus from pregnant rats is capable of producing prostanoids other than prostaglandins and their production generally parallels uterine contractile activity. Thus, the possibility that these prostanoids are involved in physiologic changes during parturition warrants further investigation.

Functional and biochemical aspects of laminaria use in first-trimester pregnancy termination

The effect of laminaria-induced cervical dilatation of plasma levels of the prostaglandin metabolite 13, 14-dihydro- 15-keto prostaglandin (PGFM) was evaluated in women undergoing elective first-trimester pregnancy termination. Seventy-one women were randomly assigned to either a treatment (n = 45) or control (n = 26) group. Cervical dilatation measured at the time of insertion of the laminaria was 3.0 +/- 0.1 mm compared to 10.2 +/- 0.2 mm at the time of removal of the laminaria 14 to 16 hours later (p less than 0.001). Peripheral levels of PGFM rose from 28.3 +/- 2.4 pg/ml (mean +/- SEM) to 43.0 +/0 2.6 pg/ml at the time of removal of the laminaria (p less than 0.001). Peripheral concentrations of PGFM in controls remained unchanged. Peripheral concentrations of PGFM did not correlate with the patient's symptoms. Although the hydrophilic property of laminaria is considered to be the principal mechanism promoting cervical dilatation, laminaria may alter the elaboration, release, or degradation of uterine prostaglandin F2 alpha. Thus, biochemical as well as mechanical factors may enhance cervical dilatation in laminaria-treated women.

Regulation of cyclic nucleotide and prostaglandin formation in normal human thyroid tissue and in autonomous nodules.

We have investigated the regulation of the human throid gland based on controls discovered in the dog thyroid gland. TSH and thyroid-stimulating immunoglobulin enhanced cAMP accumulation, which supports the validity of the Sutherland model for the action of TSH on the human thyroid. Iodide inhibited TSH- and thyroid-stimulating immunoglobulin-activated cAMP accumulation and this effect was reduced by methimazole, showing that, in this tissue, iodide, through an oxidized derivative, depresses the TSH-cAMP system. Contrary to the hypothesis of a short feedback loop of thyroid hormone, no thyroid effect of T3 or T4 was found. Adrenergic agents (norepinephrine and isoproterenol) enhanced cAMP accumulation; this effect was inhibited by dl-propranolol but not by d-propranolol or phentolamine. This suggests a positive control of the thyroid cAMP system by beta-adrenergic receptors. Histamine also increased cAMP accumulation. However, the role of these controls is unknown. Acetylcholine, by a muscarinic type effect, enhanced cGMP accumulation and prostaglandin E2 and prostaglandin F2 alpha release. These effects were mimicked by ionophore A23187 and abolished in a calcium-deprived medium, which suggests that they are secondary to a raised Ca++ influx. The results are summarized in a general working model of human thyroid regulation. These biochemical controls have been compared in normal tissue and autonomous nodules. No evidence of increased sensitivity to TSH of the nodular tissue was found. On the other hand, this tissue was less sensitive to acetylcholine (cGMP accumulation) and more sensitive to norepinephrine (cAMP accumulation).

Release of prostaglandin F2alpha during splanchnic artery occlusion shock.

Prostaglandin F2alpha concentrations were determined in hepatic portal venous plasma of dogs during splanchnic artery occlusion (SAO) shock and in nonshock control dogs. Dogs subjected to SAO shock exhibited a dramatic decrease in mean arterial blood pressure and significant increases in portal venous PGF2alpha and amino-nitrogen concentrations, as well as in cathepsin D and MDF activities. Dogs treated with indomethacin prior to SAO shock did not exhibit a significant increase in portal venous PGF2alpha. Indomethacin had no effect on the increase of plasma amino-nitrogen and only slightly reduced portal venous cathepsin D activity during SAO shock. Nevertheless, indomethacin significantly attenuated the severity of the postrelease hypotension observed in SAO shock and diminished the plasma accumulation of MDF. These studies indicate that prostaglandins are released from the splanchnic region during SAO shock and that this release can be prevented by pretreatment with indomethacin. The role of endogenously released prostaglandins in SAO shock is not clear, but the magnitude of the increase warrants further study.

Effect of intra-uterine beads alone, or combined with oestrogen treatment, on utero-ovarian venous plasma prostaglandin F2alpha and progesterone levels in the guinea-pig.

The presence of beads in the guinea-pig uterus caused premature regression of the corpora lutea, and a corresponding decrease in utero-ovarian venous plasma levels of progesterone, by days 9-10 of the oestrous cycle. If the beads were placed in one horn only, premature luteal regression occurred only in the adjacent ovary. Induced luteal regression was preceded by an increased release of prostaglandin F2alpha (PGF2alpha) from the uterine horns which contained the beads. Oestradiol benzoate treatment of guinea-pigs carrying beads in one uterine horn overcame the unilateral effect and resulted in premature luteal regression in both ovaries. This was also associated with the early release of PGF2alpha from both uterine horns, though a difference in the timing of the release was apparent between the bead-containing (experimental) and control horns.

Reduction of antigen-induced contraction of sensitized human bronchus in vitro by indomethacin.

1. Contraction of passively sensitized human bronchus induced by antigen challenge in vitro, was reduced by the prostaglandin F2alpha synthetase inhibitor, indomethacin. 2. Prostaglandin F2alpha was released during challenge and this release was inhibited by indomethacin. 3. There was a significant correlation between prostaglandin F2alpha release and antigen challenge-induced contraction, suggesting that this substance may contribute to the bronchoconstrictor response of sensitized human bronchus to antigen.