High PGE Research Articles

Growth of an implanted fibrosarcoma in rats is associated with high levels of plasma prostaglandin-E 2 and thromboxane-B 2

Growth of BN175, a malignant fibrosarcoma, was correlated with high plasma TXB 2 and PGE 2 levels. This statistically significant increase was first detected 17 days after inoculation of the tumor, at which time the tumors were 20 mms in diameter. A further increase in tumor size was associated with still higher PGE 2 and TXB 2 values. At the same time, progressive alterations in platelet function, as measured by ADP-induced platelet aggregation, were observed.6-keto-PGF 1α levels remained normal throughout the whole experiment. It was concluded that tumor growth was associated with changes in PG synthesis and platelet function, although it remains unclear whether these changes were caused by some host immunological response towards the tumor or were predominantly the result of tumor PG-synthesis.

Luteal phase variations in endogenous concentrations of prosta-glandins PGE and PGF and in the capacity for their in vitro formation in the human corpus luteum

One evidence for a luteolytic role for prostaglandin F 2α in the human is the increase in luteal PGF at times corresponding to luteolysis as reported earlier by us and other groups. There have been other contradictory reports on this point. In the present experiments we have measured the concentrations of PGE and PGF in 16 more human corpora lutea and have determined the capacity of those tissues to form PGE and PGF in vitro. PGF concentrations were highest in the mid luteal phase but were accompanied by high PGE concentrations. On the other hand, in the late luteal phase PGF concentrations, lower than in mid luteal but generally higher than in early luteal phase, were significantly higher than PGE concentrations. This pattern in PGE and PGF concentrations was also evident in the capacity of these tissues to form these compounds in vitro. In view of the known capacity of PGE 2 to counteract the luteolytic effect of PGF 2α, these variations in the relative concentrations of PGE and PGF during the luteal phase may be of significance in the process of luteolysis in the human.

Subcellular distribution of [ 3H]-prostaglandin E 2 binding sites in porcine gastric mucosa

The distribution of PGE 2 binding sites in four subcellular fractions (F1–F4) from porcine fundic mucosa obtained by gradient centrifugation was examined. Binding of HPGE 2 to fractions F2–F4 was specific, dissociable, saturable and pH dependent. A significant degree of specific binding was not evident in F1. The Scatchard analysis of binding to F2 and F3 revealed heterogenous populations of binding sites with similar dissociation constants but greater concentrations of binding sites than was evident in the initial 30,000 xg homogenate protein. A single class of low affinity binding sites was evident in F4. The ratio of total: nonspecific binding was approximately equal in F2 and F3. The ratio was considerably smaller in F4. The activity of 5' nucleotidase the marker enzyme for plasma membranes followed this ratio. There was no correlation between the binding ratio and marker enzyme activities for mitochondrial membranes and endoplasmic reticulum. These data suggest that high affinity PGE 2 binding sites occur predominantly on the plasma membrane from gastric mucosal tissue.

Comparative studies of prostaglandins F 2α and E 2 in late cyclic and early pregnant sheep: [formula omitted] synthesis by endometrium and conceptus effects of [formula omitted] indomethacin treatment on establishment of pregnancy

Endometrial concentrations of prostaglandins F 2α (PGF 2α) and E 2 (PGE 2) were measured by specific radioimmunoassay in sheep, on day 14 of estrous cycle or pregnancy, during luteolysis (Day 16 of the cycle), and after implantation (Day 23 of pregnancy) : concentrations observed on day 14 of cycle and pregnancy were similar. During luteolysis, on day 16 of cycle, a consistent drop was noticed. If luteal regression did not occur, as a consequence of the presence of an embryo, endometrial concentrations of PGF 2α on day 23, were twice those of day 14, and PGE 2 remained unchanged. In vitro 2 hour incubations of endometrial caruncular tissue from 14 days cyclic or pregnant ewes resulted in de novo synthesis of PG which could be increased by Arachidonic Acid and inhibited by Indomethacin; during the first 30 min of incubation, the PGF 2α synthesis was comparable for both endometrial tissues, whereas PGE 2 synthesis was twice as great in pregnant endometrium. Fourteen and 23 day conceptuses had high PGF 2α and PGE 2 concentrations which were not due to maternal PG sequestration : de novo PG synthesis which could be inhibited by Indomethacin was observed in incubated 14 day old embryos. Treatment of pregnant ewes from day 7 to day 22 after mating, either with Indomethacin (300 mg s.c. daily) or with Acetylsalicylic Acid (1 g I.V. daily) resulted in a sharp diminution of endometrial PG concentration and release, with no apparent effect on the establishment of pregnancy. These results tend to ascribe a less important role to PG during early pregnancy in sheep as compared with rodents, in terms of embryonic growth and implantation.

GC/MS analysis of prostaglandins in ventricular cerebrospinal fluid from head injured humans

The purpose of this study was to determine the levels of prostaglandins in ventricular cerebrospinal fluid (CSF) from severely head injured humans on successive days following injury. Sixteen samples from three patients were purified using XAD-2 and high pressure liquid chromatography and PGE 2, PGF 2α, and 6-keto-PGF 1α were quantitated utilizing deuterated internal standards and gas chromatography-mass spectrometry. Generally, the levels of PGs in ventricular CSF were found to be higher than has previously been reported for PGs in CSF from spinal taps. PG levels ranged from nondetectable to 11.8, 3.3 and 27.3 ng per ml for PGE 2, PGF 2α, and 6-keto-PGF 1α, respectively. However, in one sample, PG levels were much higher than this range and approached the levels found in human cortical tissue. Analysis of red and white blood cell numbers in the CSF sjkwed no relationship between cell numbers and prostaglandin levels. this study confirms a previous report that 6-keto-PGF 1α is the major prostaglandin in CSF and demonstrates that PG levels in ventricular CSF from head traumatized humans can be greatly elevated.

Prostaglandin production by human blood monocytes and mouse peritoneal macrophages : Synthesis dependent on in vitro culture conditions

The pattern of prostaglandin synthetase products from human peripheral blood monocytes was examined. Thromboxane and prostaglandin E were found to be the major products released by monocytes/macrophages on day one of culture following cell adherence. If these cells were studied 24h after cell adherence had occurred, then thromboxane synthesis was noted to be markedly reduced and PGE was the major secretory product. A day one type pattern, i.e. high thromboxane, high PGE could be elicited from day two cultured cells if cell adherence was delayed until day two of culture. Inflammatory stimuli caused a consistent rise in PGE release from day one and day two cultures, no consistent change in thromboxane was observed. It is suggested that activation of the thromboxane synthetase pathway in monocytes and macrophages is primarily a consequence of cell adherence. Prostaglandin E and prostacyclin (PGI) appear to be the major products released in response to inflammatory stimuli. These data demonstrate that the pattern and sequence of prostaglandins synthesized are in part a function of the in vitro culture conditions, time in culture and the species studied. Further, these findings offer a possible explanation to the discrepant reports in the literature.

Evidence for an extra-renal origin of urinary prostaglandin E 2 in healthy men

In order to verify the validity of the assumption that male urinary Prostaglandin (PG) E 2 reflects its renal production, PGE 2 and PGF 2α concentrations were measured by radioimmunoassay in the renal venous plasma (RVP) and urine (U) of 12 male and 4 female healthy volunteers. While women had a similar PGE 2/PGF 2α ratio in RVP (0.59 ± 0.18) and U (0.41 ± 0.06), men had a significantly ( p < 0.05 ) higher ratio in U (1.43 ± 1.72) as compared to RVP (0.54 ± 0.16). This was largely due to considerably higher and more variable U-PGE 2 concentrations (roughly 6 times higher than female values), despite almost identical RVP levels. The possibility of an increased U excretion of a cross-reacting member of the PG-system, as a cuase of such apparently high PGE 2-like immunoreactivity (LI), was ruled out by TLC characterization of PGE 2-LI with three different anti-PGE 2 sera. Thus, male U-PGE 2 may variably reflect an extra-renal source, such as contamination with trace amounts of seminal fluid. It is concluded that, unless such a contamination can be monitored and corrected for, measurement of male U-PGE 2 should be considered of questionable relevance to renal PG-synthesis.

Effects of methylmercuric chloride in the presence of cyclic AMP-stimulating agents on glioma and neuroblastoma cells in culture

The intracellular level of adenosine 3′, 5′-cyclic monophosphate (cyclic AMP) increased in rat glioma (C-6) and mouse neuroblastoma cells (NBP 2) after treatment with methylmercuric chloride (CH 3HgCl). The effects of CH 3HgCl in the presence of cyclic AMP-stimulating agents on glioma cells were in part different from those on NB cells. CH 3HgCl increased prostaglandin E 1 (PGE 1)-induced growth inhibition (due to reduction in cell division and cell death) in glioma and NB cells. CH 3HgCl did not reduce PGE 1-induced formation of cytoplasmic processes in glioma cells except at a higher PGE 1 concentration, but it did decrease PGE 1-induced neurite formation in NB cells. The inhibitors of cyclic nucleotide phosphodiesterase completely prevented the cytotoxic effect of CH 3HgCl on glioma cells, but they markedly enhanced the growth inhibitory effect of CH 3HgCl on NB cells.

Kallikrein, Kininogen and Kinins in Control of Blood Pressure

Plasma kallikrein releases bradykinin when activated by gram-negative septicemia or irreversible hemorrhagic shock. Pancreatitis releases glandular kallikrein causing hypotension and increased vascular permeability. Bradykinin in the brain produces hypertension. Renal kallikrein is released by high arterial pressure, vasodilators, low doses of noradrenaline, angiotensin II, mineralocorticoids and rapid volume expansion. It has a biphasic relation to sodium excretion. In essential hypertension, kallikrein release into the blood and urine is low and facilitates hypertension. High renin in Bartter's syndrome is balanced by high PGE and kallikrein without hypertension.

“Relationship between seminal PGE and 19-OH PGE and seminal fructose in man”

Seminal PGE, 19-OH PGE and fructose were assayed in normal volunteers and in infertile patients. From data obtained it appears that seminal PGE are probably not synthesized exclusively at seminal vesicles level since no relationship was observed between PGE and fructose. On the other hand the seminal vesicles appear to be the preferential site of seminal 19-OH PGE production since a close relationship was observed between 19-OH PGE and fructose in those case in which these prostaglandins were below minimum normal values. Various hypotheses are advanced in order to interpret the lack of correlation in the presence of high 19-OH PGE levels.

Prostaglandin levels in avian blood and reproductive organs.

A radioimmunoassay with a sensitivity of 5 pg/assay tube was established to measure prostaglandins E, F, and A in avian plasma and tissues. Compared to plasma values when no egg is present in the uterus (shell gland), PGE but not PGF or PGA levels were significantly higher in hens in which an egg was present (P<0.001). However, in the various segments of the oviduct as well as in the lung, PGF levels were 2–8 times higher than PGE levels. In the plasma of laying Japanese quail hens, both PGE and PGF (but not PGA) levels were significantly higher than in birds that ceased to lay. Relatively high PGE concentrations were found in turkey hens during the day (855 pg/ml), and these increased significantly in the evening (1310 pg/ml). Prostaglandin levels in the plasma of roosters were generally lower than in hen plasma. Similarly, concentrations in the testes were considerably lower than those found in ovaries. It is suggested that, in the domestic hen, E prostaglandins are involved not only in promoting oviposition (as previously proposed) but also in mobilizing calcium from skeletal stores during the hours of intensive shell formation.

ESSENTIAL FATTY ACIDS (EFA), PROSTAGLANDINS (PGS) AND HYALINE MEMBRANE DISEASE (HMD)

PGE and F exert physiological effect on the smooth muscle of blood vessels and the tracheobronchial tree; PGE dilates and F constricts. The lungs are a major site for synthesis, release and degradation of PGS. Altered PGS functions may thus contribute to the pathophysiology of HMD. 8 infants with HMD and 6 controls were studied by analyzing their plasma for PGS by radioimmunoassay, and precursor EFA by TLC and GLC. Gestational age and birth weight of sick infants were similar to controls; 31.4±4.1 vs 33.0±3.2 weeks and 1738±708 vs 1830±204 gms, respectively. Dihomo-γ-linoleic and arachidonic acids were similar in both groups. The following PGS results (mean±SD) were obtained (pg/ml). The study demonstrated: (1) plasma PGE and F are elevated in HMD as compared with controls and the ratio PGE:F is decreased; (2) upon recovery from HMD, PGE and F are elevated as compared with controls but PGE:F ratio is increased and similar to controls; (3) increased PGE level and high PGE:F ratio may contribute to the PDA.

Prostaglandin E 1 specific binding in rhesus myometrium

Myometrial low speed supernatant prepared from non-pregnant rhesus uteri was incubated with 3H-Prostaglandin (PG)E 1 with or without addition of unlabelled prostaglandins. The uptake of 3H-PGE 1 was inhibited in a dose dependent fashion by PGE 2>PGE 1>PGA 1>PGF 2α=PGA 1>PGB 1=PGB 2≥PGD 2. PGE 1 metabolites inhibited 3H-PGE 1 binding in the following order: 13,14-dihydro-PGE 1>13,14-dihydro-15-keto-PGE 1=15-keto-PGE 1. The specific binding of 3H-PGE 1 and 3H-PGF 2α was similarly affected by the temperature and time of incubation. Equilibrium binding constants determined using rhesus uteri obtained during the luteal phase of the menstrual cycle indicate the presence of high affinity PGE 1 binding sites with an average (n=3) apparent dissociation constant of 2.2 × 10 −9M and a lower affinity PGE 1 binding site with a K d ≅ 1 × 10 −8M. No high affinity — low capacity 3H-PGF 2α sites could be demonstrated. Relative uterine stimulating potencies of some natural prostaglandins and prostaglandin analogs tested after acute intravenous administration in mid-pregnant rhesus monkeys corresponded with the PGE 1 binding inhibition of the respective compound. The uterine stimulating potencies of the prostaglandin analogs tested were: (15S)-15-methyl-PGE 2=16,16-dimethyl-PGE 2>17-phenyl-18,19,20-trinor-PGE 2>16 phenoxy-17,18,19,20-tetranor-PGF 2α=PGE 2=PGE 1=(15S)-15-methyl-PGF 2α>PGF 2α.

Prostaglandin E 1 specific binding in rhesus myometrium

Myometrial low speed supernatant prepared from non-pregnant rhesus uteri was incubated with 3H-Prostaglandin (PG) E 1 with or without addition of unlabelled prostaglandins. The uptake of 3H-PGE 1 was inhibited in a dose dependent fashion by PGE 2>PGE 1>PGA 1>PGF 2α=PGA 1>PGB 1=PGB 2≥PGD 2. PGE 1 metabolites inhibited 3H-PGE 1 binding in the following order: 13,14-dihydro-PGE 1>13,14-dihydro-15-keto-PGE 1=15-keto-PGE 1. The specific binding of 3H-PGE 1 and 3H-PGF 2α was similarly affected by the temperature and time of incubation. Equilibrium binding constants determined using rhesus uteri obtained during the luteal phase of the menstrual cycle indicate the presence of high affinity PGE 1 binding sites with an average (n=3) apparent dissociation constant of 2.2 × 10 −9M and a lower affinity PGE 1 binding site with a K d ≊ 1 × 10 −8M. No high affinity — low capacity 3H-PGF 2α sites could be demonstrated. Relative uterine stimulating potencies of some natural prostaglandins and prostaglandin analogs tested after acute intravenous administration in mid-pregnant rhesus monkeys corresponded with the PGE 1 binding inhibition of the respective compound. The uterine stimulating potencies of the prostaglandin analogs tested were: (15S)-15-methyl-PGE 2=16,16-dimethyl-PGE 2>17-phenyl-18,19,20-trinor-P GE 2>16 phenoxy-17,18,19,20-tetranor-PGE 2α=PGE 2=PGE 1=(15S)-15-methyl-PGE 2α>PGF 2α.