The concentrations of 6-keto-PGF1 alpha and TXB2 in plasma samples from patients with benign and malignant tumours of the breast

Peripheral plasma concentrations of 6-keto-PGF1 alpha and TXB2 were measured in patients with benign and malignant tumours of the breast, in patients with non-gynecological diseases, and in healthy female controls. The values were significantly higher in female patients with malignant tumours of the breast than in healthy controls (146 +/- 28 vs 13 +/- 2.5 pg/ml for 6-keto-PGF1 alpha p less than 0.01 and 78 +/- 17 vs 11 +/- 2 pg/ml for TXB2, p less than 0.01). Benign tumours of the breast were also associated with significantly raised plasma levels of 6-keto-PGF1 alpha and TXB2 compared to normal controls (52 +/- 5 vs 13 +/- 2.5 pg/ml for 6-keto-PGF1 alpha, p less than 0.01 and 26 +/- 5 vs 11 +/- 2 pg/ml for TXB2, p less than 0.05). The high levels of 6-keto-PGF1 alpha and TXB2 were not found to be correlated with clinical and histopathological data. The surgical removal of the primary tumour has apparently no effect on the plasma concentrations of 6-keto-PGF1 alpha and TXB2 over a follow-up period of 9 days after operation. The lack of alterations in the ratio of TXB2:6-keto-PGF1 alpha in the cancer patients and other subjects studied before and after surgery is indicative of the regulatory power of metabolic systems to preserve the homeostatic balance.     

Prostaglandin F2 alpha-stimulated release of ovarian oxytocin in the sheep in vivo: threshold and dose dependency

To determine the threshold of prostaglandin F2 alpha (PGF2 alpha)-stimulated oxytocin secretion from the ovine corpus luteum, low levels of PGF2 alpha (5-100 pg/min) were infused into the ovarian arterial blood supply of sheep with ovarian autotransplants. PGF2 alpha was infused for six sequential 10-min periods at hourly intervals, 6, 12, or 24 days after estrus (n = 3 for each day). Each cycle day was studied during a separate cycle. Oxytocin and progesterone in ovarian venous and carotid arterial plasma was measured by radioimmunoassay, and secretion rates were determined (venous-arterial concentration x plasma flow). In animals treated on Day 6, 5 pg/min PGF2 alpha caused a significant release of oxytocin (p less than 0.01), whereas in animals treated on Day 12, this threshold was 40 pg/min (p less than 0.05). In animals treated on Day 24, the threshold for oxytocin release was greater than 100 pg/min. PGF2 alpha did not significantly change ovarian blood flow or progesterone secretion rate on any day (p greater than 0.05). To determine residual luteal oxytocin after each threshold experiment, 5 mg PGF2 alpha was given i.m. to all animals. Significantly more oxytocin was released by Day 6 than by Day 12 and Day 24 corpora lutea, and by Day 12 than by Day 24 corpora lutea (1.2 micrograms, 0.7 microgram, and 0.3 microgram, respectively; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Interleukin-2 enhances the release of endothelin-1 from the rat mesenteric artery

We measured the ET-1 concentration in plasma and in the perfusate of the mesenteric arteries of rats treated with a therapeutic dose of IL-2 for 7 days (100000 U/Kg, iv.). The plasma ET-1 concentration in rats given IL-2 was 14.2 +/- 3.2 pg/ml which was significantly greater than that in the controls (2.5 +/- 0.4 pg/ml, P less than 0.05). The mesenteric arteries also released a significantly greater amount of ET-1 (29.5 +/- 1.6 pg/h) than that in controls (16.8 +/- 2.3 pg/h, P less than 0.01). The arterial blood pressure was significantly lower after IL-2 treatment than the pre-dosing level (P less than 0.05). It is concluded that IL-2 induces ET-1 release from the vascular wall, possibly as a result of reversible endothelial dysfunction caused by IL-2.     

Comparison of plasma prostanoid levels in the human cord artery in normal and fetal distressed deliveries

Prostaglandin E2 (PGE2), thromboxane B2 (TXB2; as a stable metabolite of TXA2), prostaglandin F2 alpha (PGF2 alpha) and 6-keto-PGF1 alpha (as a stable end product of prostacyclin) have been measured by using specific radioimmunoassay in the plasma of the cord artery immediately after delivery before the cord was clamped. Plasma prostanoid concentrations in normal deliveries (n = 8, as controls) were 24.8 +/- 2.6 (PGE2), 246.8 +/- 37.0 (TXB2), 122.2 +/- 13.3 (PGF2 alpha) and 82.1 +/- 7.7 (6-keto-PGF1 alpha) respectively (pg/ml, mean +/- s.e). On the other hand, in fetal distressed deliveries showing continuous bradycardia (n = 6), they increased significantly to 275.4 +/- 20.1 (PGE2), 948.6 +/- 102.5 (TXB2), 218.0 +/- 21.4 (PGF2 alpha) and 1498.6 +/- 298.4 (6-keto-PGF1 alpha) respectively (pg/ml, mean +/- s.e, p less than 0.005). However, both PGF2 alpha/PGE2 and TXB2/6-keto-PGF1 alpha ratios declined significantly from 4.70 +/- 0.33 to 0.68 +/- 0.05 and from 3.07 +/- 0.37 to 0.68 +/- 0.12 respectively (mean +/- s.e, p less than 0.005) in the fetal distressed group compared with those of the controls. From these results, it may be concluded that the cord artery, which is known as the patent source for the production of PGE2 and prostacyclin, did exert a sufficiently strong reaction to overcome the undesirable haemodynamic changes to maintain the fetal well-being in utero.     

Plasma thromboxane and prostacyclin: comparison during normal pregnancy and pregnancy complicated by hypertension

Plasma levels of thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), stable metabolites of two prostanoids with opposing biological effects, TXA2 and prostacyclin, were measured by radioimmunoassay in normal pregnancy (controls) and pregnancy complicated by hypertension (PIH) from 32 to 36 (Period 1; P1) and from 36 to 40 (Period 2; P2) weeks of gestation. The plasma concentration of each compound in the control subjects was 265.6 +/- 58.4 (TXB2), 132.4 +/- 16.5 (6-keto-PGF1 alpha) for P1 (n = 10) and 142.6 +/- 11.8 (TXB2), 68.5 +/- 5.2 (6-keto-PGF1 alpha) for P2 (n = 10) respectively (pg/ml, mean +/- s.e). In the patients with PIH, TXB2 concentrations increased moderately for P1 (419.2 +/- 21.2; n = 7) and significantly (p less than 0.005) for P2 (452.8 +/- 31.0; n = 7) respectively (pg/ml, mean +/- s.e), while the plasma levels of 6-keto-PGF1 alpha revealed a slight to moderate decrease both for P1 (84.5 +/- 4.0; n = 7) and P2 (59.7 +/- 8.1; n = 7) respectively (pg/ml, mean +/- s.e). The physiological balance of TXB2 to 6-keto-PGF1 alpha was significantly greater (p less than 0.005) in the patients with PIH, where the TXB2/6-keto-PGF1 alpha ratio was 5.2 +/- 0.7 for P1 and 9.4 +/- 2.3 for P2 respectively (mean +/- s.e) compared with that of the controls, where it was 2.4 +/- 0.4 for P1 and 2.0 +/- 0.2 for P2 respectively (mean +/- s.e).(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of umbilical vein models for measurement of relative prostacyclin and thromboxane production

There is growing evidence that blood vessels generate TXA2 in addition to PGI2. We examined effluents from continuously perfused human umbilical vein and supernatants from umbilical vein rings for TXB2 and 6-keto-PGF1 alpha measurements (stable metabolites of TXA2 and PGI2, respectively). TXB2 and 6-keto-PGF1 alpha were identified in all samples. 6-keto-PGF1 alpha to TXB2 ratio was higher in intact vein effluents than in the venous ring supernatants (112:1 and 28:1, respectively, P less than 0.01). Arachidonate stimulation increased 6-keto-PGF1 alpha and TXB2 levels similarly in the intact vein effluent. In contrast, stimulation of the venous rings resulted in a relatively larger increase in TXB2 than in 6-keto-PGF1 alpha. This caused 6-keto-PGF1 alpha to TXB2 ratio to decline (p less than 0.01). The identity of TXB2 was confirmed in several different ways. These data suggest that 1) human umbilical veins produce TXA2 in addition to PGI2, 2) TXA2 release is more by venous rings than by the intact vein probably reflecting contribution from non-endothelial layers, and 3) arachidonate stimulation causes relatively greater release of TXA2 than of PGI2 from the venous rings, whereas release of PGI2 and TXA2 is similar from the intact vein.     

Production of endothelin-1 from the mesenteric arteries of streptozotocin-induced diabetic rats

Release of endothelin-1 (ET-1) from the mesenteric arteries of Wistar rats with streptozotocin-induced diabetes (STZ-DM) rats and nondiabetic rats was measured by a specific enzyme immunoassay following purification using an immunoaffinity column. The mesenteric arteries from STZ-DM rats released a significantly higher amount of ET-1 as compared to control rats (35.8 +/- 2.8 vs 14.9 +/- 2.0 pg/1hr, p less than 0.05). The plasma level of ET-1 in STZ-DM rats was also elevated to a significant extent as compared to controls (5.1 +/- 0.4 vs 3.0 +/- 0.4 pg/ml, p less than 0.05). The systolic blood pressure of STZ-DM rats was significantly higher than of the controls (p less than 0.05). The increased level of plasma ET-1 as well as its release from the mesenteric artery of STZ-DM rats may suggest its release following damage to the endothelium caused by diabetes and/or by associated changes in blood pressure.     

Impaired function of alpha2-adrenergic autoreceptors on sympathetic nerves associated with mesenteric arteries and veins in DOCA-salt hypertension

The present study tested the hypothesis that there is impaired function of alpha(2)-adrenergic autoreceptors and increased transmitter release from sympathetic nerves associated with mesenteric arteries and veins from DOCA-salt rats. High-performance liquid chromatography was used to measure the overflow of ATP and norepinephrine (NE) from electrically stimulated mesenteric artery and vein preparations in vitro. In sham arteries, nerve stimulation evoked a 1.5-fold increase in NE release, whereas in DOCA-salt arteries there was a 3.9-fold increase in NE release over basal levels (P < 0.05). In contrast, stimulated ATP release was not different in DOCA-salt arteries compared with sham arteries. In sham veins, nerve stimulation evoked a 2.9-fold increase in NE release, whereas in DOCA-salt veins there was a 8.4-fold increase in NE release over basal levels (P < 0.05). In sham rats NE release, normalized to basal levels, was greater in veins than in arteries (P < 0.05). The alpha(2)-adrenergic receptor antagonist yohimbine (1 microM) increased ATP and NE release in sham but not DOCA-salt arteries. The alpha(2)-adrenergic receptor agonist UK-14304 (10 microM) decreased ATP release in sham but not DOCA-salt arteries. In sham veins, UK-14304 decreased, but yohimbine increased, NE release; effects that were not observed in DOCA-salt veins. These data show that nerve stimulation causes a greater increase in NE release from nerves associated with veins compared with arteries. In addition, impairment of alpha(2)-adrenergic autoreceptor function in sympathetic nerves associated with arteries and veins from DOCA-salt rats results in increased NE release.     

Production of prostacyclin, 6-keto-PGF1 alpha and thromboxane B2 by incubated samples of umbilical vessels: a comparison of methods for expressing the results on dry weight, wet weight, protein or DNA bases

The production of PGI2 (determined by bioassay), and of 6-keto-PGF1 alpha and TXB2 (determined by radioimmunoassay) by samples of human umbilical vessels have been measured. The results have been calculated on four bases: dry weight, wet weight, protein and DNA. There was a higher production of PGI2 and 6-keto-PGF1 alpha by umbilical veins than by umbilical arteries; no significant difference in TXB2 production was observed between umbilical veins and arteries. The ratio of 6-keto-PGF1 alpha: TXB2 production was about 100 for the samples of veins and about 40 for the samples of arteries. The best methods of expressing the results were on the bases of protein and DNA, the latter basis being marginally the best. The least satisfactory method for expressing the results was that based on dry weight. The physiological and practical implications of the results are discussed.     

Prostaglandin F2 alpha as the luteolysin in swine: VI. Hormonal regulation of the movement of exogenous PGF2 alpha from the uterine lumen into the vasculature

To test the endocrine-exocrine theory of maternal recognition of pregnancy in the pig 16 gilts were assigned randomly to a 2 X 2 factorial involving pretreatment with sesame oil (SO) or estradiol valerate (5 mg; EV) injected on Days 11 through 14 of the estrous cycle and an intrauterine injection of saline (5 ml; SA) or prostaglandin F2 alpha (50 micrograms; PGF) on Day 14. Peripheral blood samples were collected for 120 min postinjection and analyzed for 15-keto-13,14-dihydro-PGF2 alpha (PGFM). PGFM concentrations were lower in EV than SO gilts (438 vs. 844 pg/ml; p less than 0.05). There was heterogeneity of regression between EV and SO gilts (p less than 0.01), with EV gilts having a slower release of PGF from the uterine lumen into the vasculature. Prostaglandin F2 alpha did not increase mean PGFM concentrations (p greater than 0.10), but resulted in an altered temporal pattern of PGFM (p less than 0.05) compared to SA gilts. There was an interaction between the two treatments over time, with EV-PGF gilts demonstrating a slower, more gradual release of PGFM than SO-PGF gilts. To test whether prostaglandins of the E series were involved in this mechanism, gilts were assigned to two 4 X 4 latin squares balanced for residual effects and treated with saline or flunixen meglumine (Banamine). Each gilt was treated with four PGE:PGF infusion sequences (SEQ) in each uterine horn: phosphate-buffered saline (PBS; PBS-SEQ), PGE1 (50 micrograms), PGE2 (50 micrograms), and PGE1 (25 micrograms) + PGE2 (25 micrograms) (PGE-SEQ), with each infusion followed 15 min later by PGF (25 micrograms).(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

水钠负荷对血,肾脏前列环素,血栓素A2的影响及...

For evaluating the role of prostacyclin (PGI2) and thromboxane A2 (TXA2) in the metabolism of salt and water, the metabolic products of PGI2 and TXA2 (6-keto-PGF1 alpha and TXB2 respectively) were measured by radioimmunoassay in salt-loaded rabbits. 36 normal rabbits were randomly divided into 3 groups: 1. normal control group; 2. 3h salt-loading group (3 h group); 3. 24 h salt-loading group (24 h group). Both the 3 h and 24 h groups were given 0.9% NaCl solution by subcutaneous injection to the hind legs. The kidneys were dissected into 4 slices: outer cortex, inner cortex, outer medulla and inner medulla. The plasma 6-keto-PGF1 alpha in the 3 h group was increased from the control value of 46.61 +/- 19.04 pg/ml to 111.63 +/- 58.36 pg/ml (P less than 0.01). All of the dissected renal slices also showed significant increase of 6-keto-PGF1 alpha synthesis in both the 3 h and the 24 h groups (P less than 0.001 vs. normal). The urinary sodium concentrations have a good correlation with 6-keto-PGF1 alpha in plasma or in kidney tissues. Plasma TXB2 in normal group was 499.27 +/- 197.86 pg/ml, but no significant change was found in the 3h group. However, in the 24 h group it decreased significantly to 218.76 +/- 114.54 pg/ml (P less than 0.05 vs. normal group). Although the TXB2 increment was significant only in inner medulla, all other dissected renal slices showed some increase of TXB2 synthesis too. It is concluded that salt-loading can cause increase of PGI1 and TXA2 synthesis in normal renal tissues.(ABSTRACT TRUNCATED AT 250 WORDS)     

Endothelin-1 and endothelin-3 stimulate prostaglandin E2 secretion from the rat median eminence.

The in vitro effects of endothelin-1 (ET-1) and endothelin-3 (ET-3) on the release of prostaglandin (PG)E2 from the rat median eminence were investigated. The addition of ET-1 from 10(-9) M to 10(-6) M stimulated PGE2 release in a dose-dependent manner (from 10.5 +/- 2.1 to 54.4 +/- 5.6 pg/ME fragment/30 min; mean +/- SEM, p less than 0.001). ET-3 also stimulated the release of PGE2 from 10(-7) M to 10(-5) M dose dependently (from 18.1 +/- 0.7 to 60.9 +/- 17.4 pg/ME fragment/30 min p less than 0.05). The time course effect of ET-3 (10(-6) M) showed that PGE2 release was stimulated within five minutes (control, 1.5 +/- 0.5; ET-3, 15.8 +/- 3.0 pg/ME fragment/5 min, p less than 0.01). These results suggest that ET-1 and ET-3 have some physiological effects on the rat median eminence.     

Plasma 6-keto-PGF1 alpha, thromboxane B2 and PGE2 during diabetic ketoacidosis

In 10 patients admitted to hospital with diabetic ketoacidosis plasma prostanoids 6-keto-PGF alpha, thromboxane B2 and PGE2 were studied before treatment and following recovery. During ketoacidosis the median plasma 6-keto-PGF1 alpha and PGE2 were significantly increased compared to those of a normal reference group: 5.2 pg/ml and 3.9 pg/ml versus 1.7 pg/ml and 0.4 pg/ml (p less than 0.01 and p less than 0.05). In response to therapy both prostanoids decreased significantly towards a normal level, 6-keto-PGF1 alpha: 0.5 pg/ml p less than 0.01 and PGE2: 0.08 p less than 0.05 respectively. The changes in plasma 6-keto-PGF1 alpha were negatively correlated to changes in pH, rho: -0.7788 p = 0.0135, whereas the changes in PGE2 were positively correlated to serum creatinine at admittance, rho: 0.6976, p = 0.0368 and to the amount of intravenous fluid and insulin used during treatment, rho: 0.7500 p = 0.0126 and rho: 0.8424, p = 0.0023 respectively. Plasma thromboxane B2 concentrations were not elevated and did not change after treatment of the ketoacidosis.     

Leukotrienes increase levels of prostanoids in cerebrospinal fluid in piglets

We investigated effects of exogenous leukotrienes (C4, D4, or E4) on levels of prostanoids in cerebrospinal fluid in newborn pigs (1-5 days). A "closed" cranial window was placed over the parietal cortex. Pial arterial diameter was measured with a microscope and electronic micrometer system. Levels in cerebrospinal fluid (CSF) of 6-keto-Prostaglandin F1 alpha (6-keto-PGF1 alpha), Thromboxane B2 (TXB2), and Prostaglandin E2 (PGE2) were measured by radioimmunoassay. Topical application of leukotrienes C4, D4, or E4 (5,000 ng/ml) similarly constricted pial arteries by 15 +/- 2% (n = 14) (mean +/- SEM). In addition, leukotrienes increased levels of 6-keto-PGF1 alpha from 806 +/- 136 to 1,612 +/- 304 pg/ml (n = 13), TXB2 from 161 +/- 31 to 392 +/- 81 pg/ml (n = 10), and PGE2 from 2,271 +/- 342 to 4,636 +/- 740 pg/ml (n = 13). Each type of leukotriene had similar effects on prostanoid synthesis. In other experiments (n = 5), we found that 2.0 ng/ml PGE2 in CSF dilated pial arteries by 24 +/- 8% and that 1.0 ng/ml PGI2 dilated pial arteries by 15 +/- 6%. These results indicate that leukotrienes are able to increase levels of prostanoids in cerebral cortex.     

Effect of pregnancy-specific protein B on prostaglandin F2 alpha and prostaglandin E2 release by day 16-perifused bovine endometrial tissue

Five normal estrous cycling multiparous non-lactating Brahman cows were utilized to determine if pregnancy-specific protein B (PSPB) would alter prostaglandin F2 alpha (PGF) and prostaglandin E2 (PGE) synthesis/release by endometrial tissue. The uterine horn ipsilateral to the corpus luteum was excised on Day 16 of the estrous cycle. Endometrial tissue (200 mg wet wt) was cultured in Nutrient Mixture F-10 medium in a perifusion system. The tissue and medium were aerated with 95% O2: 5% CO2 and temperature was maintained at 39 degrees C. The medium flow rate was 100 microliters/min and fractions were collected at 20 min intervals. After a 120 min settling period, tissue culture continued with: 1) control (medium only); 2) 2 micrograms [Asu1,6]-oxytocin/ml medium for 1 h; 3) 4 or 8 micrograms PSPB/ml medium for 2 h; or 4) 4 or 8 micrograms PSPB/ml medium for 2 h plus 2 micrograms oxytocin/ml medium during the second h. Differences in PGF and PGE secretion rate were not found between 4 and 8 micrograms PSPB. Therefore, groups were combined and data were analyzed according to tissue not receiving PSPB (control); receiving PSPB and receiving PSPB plus oxytocin. A nonsignificant rise (p greater than 0.10) in PGF secretion was observed in response to PSPB and PSPB plus oxytocin above the control by the end of the perifusion period (263.7 +/- 41.7, 220.0 +/- 41.7 and 166.1 +/- 41.7 pg/(100 mg tissue/min), respectively). Treatment with PSPB alone elevated (p less than 0.05) PGE secretion rate above control by 100 and 160 min post-removal of PSPB treatment. Treatment with PSPB plus oxytocin elevated (p less than 0.05) PGE release above control by 20 min after starting oxytocin treatment and continued throughout the duration of the perifusion. Pregnancy-specific protein B plus oxytocin-induced PGE release was greater (p less than 0.05) than PSPB alone after initiating the oxytocin treatment until 20 min after removal of the treatments. However, no further differences between PSPB alone and PSPB plus oxytocin treatments were detected throughout the remainder of the perifusion period. It appears that PSPB tends to elevate PGF release and significantly elevates PGE release from Day 16 endometrial tissue.     

Effect of vasodilator prostaglandins on the vascular renin-angiotensin system

The interaction of prostaglandin (PG) with the vascular renin-angiotensin (R-A) system was examined by studies on the effects of PGI2, PGE2 and the inhibitor of PG synthesis, indomethacin, on the release of angiotensin II (Ang II) from isolated rat mesenteric arteries. The Ang II released from the vasculature was measured after its concentration in a Sep-Pak C18 cartridge connected to the perfusion system. After perfusion with drugs, the specific vascular renin activity inhibited by anti-renin antibody was determined. The basal perfusion pressure was constant (19.6 +/- 1.1 mmHg) at a flow rate of 4.5 ml/min, and was not changed by any of these drugs. The basal levels of Ang II release and vascular renin activity were 44 +/- 5 pg/30 min and 113 +/- 8 pg Ang I/mg protein/hr, respectively. Infusion of PGI2 (10(-6) M) significantly decreased both Ang II release (p less than 0.01) and vascular renin activity (p less than 0.05) as compared with the control levels. Infusion of PGE2 (10(-6) M) decreased Ang II release significantly (p less than 0.05) and vascular renin activity slightly. Infusion of indomethacin (10(-6)M) increased vascular renin activity significantly (p less than 0.01). Pretreatment with indomethacin (10 mg/kg, ip) for 2 days also increased vascular renin activity (p less than 0.01). These results indicate that in contrast to their effects on the renal R-A system, PGs suppress the vascular R-A system and that these two local vasoactive factors interact to regulate vascular tone.     

Anhydrolevuglandin D2 inhibits the uterotonic activity of prostaglandins F2 alpha and D2

Anhydrolevuglandin D2 (AnLGD2), which is produced from PGH2 by a water-induced rearrangement and subsequent dehydration, is uterotonic. However, increasing concentrations caused decreased responses of the uterine horns. AnLGD2 inhibited responses of uteri to stimulation by specific prostaglandins. PGF2 alpha was inhibited at an AnLGD2:PGF2 alpha ratio of 0.05:1 with 5 to 25 pg/ml concentrations of PGF2 alpha. The response to PGD2 was inhibited at an AnLGD2:PGD2 ratio of 0.05:1 with PGD2 concentrations of 5 to 75 pg/ml. In contrast, the uterotonic effects of PGE2 were not inhibited by AnLGD2. When AnLGD2 was added to baths with contracting uteri it inhibited contractions less if the exposure period was 5 min than if it was 10 min. The longer exposure times produced prolonged inhibition of contractile activity with bath concentrations of AnLGD2 as little as 2.5 pg/ml.     

Secretion of oxytocin and progesterone by ovine corpora lutea in vitro

The mechanisms involved in the control of oxytocin and progesterone secretion by the ovine corpus luteum have been investigated in vitro using luteal slice incubations. Oxytocin and progesterone were secreted at constant rates from luteal slices for 2 h of incubation (366 +/- 60 pg X mg X h and 18.9 +/- 0.18 ng X mg X h, respectively). Secretion of progesterone, but not of oxytocin, was significantly (p less than 0.02) stimulated in the presence of ovine luteinizing hormone. Incubation of luteal slices in medium containing 100 mM potassium, however, resulted in increased secretion of oxytocin and, to a lesser extent, of progesterone (294 +/- 59% and 142 +/- 15%, respectively, p less than 0.05). Basal oxytocin secretion was reduced during incubation in calcium-free medium, compared to secretion in the presence of calcium (70 +/- 15 and 175 +/- 25 pg X mg X 20 min, respectively, p less than 0.01), whereas progesterone secretion was not altered in the absence of calcium. Secretion of both hormones by luteal slices was stimulated by the addition of the calcium ionophore A23187 (p less than 0.05). Addition of prostaglandin F2 alpha (2.8 microM) had no effect on secretion of either oxytocin or progesterone. We have demonstrated that oxytocin and progesterone can be stimulated, independently, from corpus luteum slices incubated in vitro. The pattern of release is consistent with the proposal that oxytocin, but not progesterone, is associated with and actively released from luteal secretory granules. Our results also indicated that prostaglandin F2 alpha does not directly stimulate release of oxytocin or progesterone from luteal cells in vitro.     

T-2 toxemia and brain prostaglandins

T-2 toxin is a trichothecene mycotoxin which is a member of a family of closely related sesquiterpenoids. It was recently shown that T-2 toxemia is associated with elevated plasma levels of eicosanoids. To study further the effect of T-2 on the cyclooxygenase pathway of arachidonate we examined the release of PGE2, TXB2 and 6-keto-FGF1 alpha from brain tissue exposed to T-2 toxin in vivo or in vitro. Administration of T-2 toxin (0.75 or 2 mg/kg) to conscious rats caused a transient increase in the rate of the release of 6-keto-PGF1 alpha and TXB2 from brain slices taken from the cortex (C); no effect was found in the hypothalamus (HT) or the nucleus tractus solitarius (NTS) region of the medulla oblogata. PGE2 showed time and dose related increments (over 5 folds) in both the C and HT but not in the NTS. Incubation of cortical or hypothalamic slices in oxygenated Krebs buffer with a wide range of T-2 toxin concentrations (10(-9)-10(-3) M) demonstrated a complex response: stimulation of PGE2 and TXB2 release from C slices at 10(-7) M (greater than 40%, p less than 0.01 and 20%, p less than 0.05, respectively) and inhibition at high concentrations (greater than 10(-4) M) of all PGs studied. Hypothalamic slices showed decrease in all PGs released by very low (10(-9)-10(-8)) or very high (10(-4) M) concentrations of T-2. These studies are consistent with the possibility that the arachidonate cascade in the central nervous system might have a role in the pathophysiology of trichothecene mycotoxicosis.