Biomedical subjects

D M Olson

Publications and source records attributed to D M Olson.

At least 73 records · Page 4Linked to original sources

PubMed1990

Liposome-mediated augmentation of antioxidant defenses in fetal rat pneumocytes.

Cultured pneumocytes, prepared from fetal rat lung, are growth inhibited and have increased lactate dehydrogenase release and prostaglandin synthesis in response to 50 and 95% O2 exposure. The uptake of cationic liposomes by these fetal cells is more rapid and extensive than is the case with cultured adult pneumocytes. Protection of fetal pneumocytes against the cytotoxic effects of 50 or 95% O2 by liposome-entrapped antioxidant enzymes requires a liposome phospholipid concentration of only 1 nmol/cm2, compared with 45 nmol/cm2 for adult cells, which is a cytotoxic phospholipid concentration for the fetal cells. Despite this capacity of low concentrations of liposomes containing superoxide dismutase and catalase to increase endogenous antioxidant enzyme content, and to protect against cell death, such treatment does not attenuate O2-mediated alterations of cell growth or prostaglandin release. Inhibition of pneumocyte DNA synthesis, by elevated O2 concentrations, cannot be attributed to an autocrine effect of enhanced prostaglandin synthesis, because the addition of 50 microM ibuprofen to inhibit prostaglandin synthesis does not prevent O2-mediated effects on DNA synthesis.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed1990

Stimulation of prostaglandin synthesis by hyperoxia in perinatal rat lung cells.

Prostaglandins (PGs) have been implicated in the development of pulmonary oxygen toxicity. We tested the hypothesis that hyperoxia modulates PG synthesis in a differentiation-arrested primary lung cell culture model in the rat at three developmental ages: day-20 gestation (term = 22 days), days 1 and 3 after birth. The time courses of the response to hyperoxia were defined in preconfluent lung cells as well as in growth-arrested, confluent cells. From days 4-8 after plating in growth medium containing 10% carbonstripped fetal bovine serum, exposure to 95% O2, in contrast to 1% O2, inhibited cell proliferation but significantly enhanced the production of PGI2 and, to a lesser extent, PGE2 at all three ages. The capacity to metabolize exogenous arachidonic acid (AA) to PGI2 was also increased two-to threefold (P less than 0.01). Cellular release of lactate dehydrogenase, a measure of O2 toxicity, remained unchanged during exposure to 1% O2 but increased fivefold between 48 and 96 h after exposure to hyperoxia (from 2% total to 10.5%, P less than 0.01). In confluent, growtharrested cells, under serum-free conditions, exposure to hyperoxia for 24-48 h resulted in a similar induction of PG synthesis. Our results suggest that hyperoxia stimulates PG synthesis in the perinatal rat lung and that this effect is independent of cell growth or the presence of serum. We speculate that this hyperoxia-induced PG synthesis is a relatively early response to oxidant stress and may serve as an useful early marker for O2 toxicity in perinatal lung cells.

Animals↗

PubMed1990

Arachidonic acid release from cultured human amnion cells: the effect of dexamethasone.

Glucocorticoids inhibit prostaglandin (PG) synthesis in several cell types, presumably by inhibiting arachidonic acid (AA) deacylation from phospholipids. We studied the effects of glucocorticoids on cultured term human amnion cell AA release. Confluent monolayer cultures of amnion cells were adapted to serum-free medium, and phospholipids were labeled for 18 h with [14C]AA. The calcium ionophore A23187 (0.2-5.0 mumol/L) stimulated [14C]AA release (up to 2.2-fold) in a dose- and time-dependent manner. The apparent sources of the liberated [14C]AA were phosphatidylcholine and phosphatidylethanolamine. Pretreatment for 24 h with the synthetic glucocorticoid dexamethasone (0.1-1000 nmol/L) significantly inhibited (P less than 0.01) basal (unstimulated) [14C]AA release by 69% in subsequent 1-h experiments. The sole apparent source of free [14C]AA during this inhibitory state was phosphatidylethanolamine. Dexamethasone pretreatment slightly inhibited (13%; P less than 0.05) calcium ionophore-stimulated [14C]AA release; however, it was still 3.8-fold greater than basal release, suggesting that the glucocorticoid effect on stimulated AA release was not biologically relevant. Further characterization of the glucocorticoid effect revealed that preincubation of the cultures with dexamethasone for as little as 20 min inhibited basal [14C]AA release. Furthermore, studies involving actinomycin-D and cycloheximide demonstrated that inhibition of RNA and protein synthesis failed to block the glucocorticoid inhibition of basal AA liberation. The glucocorticoid receptor antagonist RU 38486, alone or in the presence of dexamethasone, also inhibited unstimulated [14C]AA release. Cortisol, dehydroisoandrosterone sulfate, 17 beta-estradiol, and progesterone all inhibited basal [14C]AA liberation. We conclude that glucocorticoids inhibit unstimulated AA release from cultured amnion cells, but do not prevent calcium ionophore from stimulating a large increase in AA release.(ABSTRACT TRUNCATED AT 250 WORDS)

Amnion↗

PubMed1989

Production of prostaglandins by fetal rat lung type II pneumonocytes and fibroblasts.

The output of prostaglandins I2, E2, F2 alpha and 13,14-dihydro-15-keto-PGF2 alpha (PGFM) from third passage day 20 rat fetal fibroblasts and type II alveolar pneumonocytes was studied. In 2 h incubations, the output levels for each cell type were: PGI2 greater than PGE2 much greater than PGF2 alpha = PGFM when cells were incubated with Ca2+ ionophore A23187 (10 microM) or arachidonic acid (1 microgram/ml).

Animals↗

PubMed1989

Effects of reactive oxygen species on prostacyclin production in perinatal rat lung cells.

A differentiation-arrested primary cell culture model was used to examine the role of reactive oxygen species in the control of prostacyclin (PGI2) production in the perinatal rat lung. Coincubation of the lung cells with arachidonic acid (AA) and xanthine (X, 0.25 mM) plus xanthine oxidase (XO, 10 mU/ml) or with AA and glucose (25 mM) plus glucose oxidase (25 mU/ml) augmented the AA-induced PGI2 output. Superoxide dismutase (10 U/ml) did not alter the X + XO effect, whereas catalase (10 U/ml) eliminated both X + XO and glucose plus glucose oxidase effects. H2O2 (1-200 microM) showed a dose-related biphasic augmentation with peak stimulation at 20 microM. Catalase again blocked this effect, but dimethylthiourea, a hydroxyl radical scavenger, did not. A 20-min pretreatment of the cells with X + XO, glucose plus glucose oxidase, or H2O2, however, diminished the capacity of the cells to convert exogenous AA to PGI2. This pretreatment effect was also blocked by catalase. The responses were similar in lung cells obtained from day 20 rat fetuses (term = 22 days) and 1-day-old newborn rats. Lactate dehydrogenase release was not detected during treatment periods but increased significantly after exposure to reactive oxygen species.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗

PubMed1989

Dexamethasone stimulates arachidonic acid conversion to prostaglandin E2 in human amnion cells.

The purpose of this investigation was to study the mechanism of stimulation of PGE2 output from human amnion epithelial cells by the synthetic glucocorticoid dexamethasone. Cells incubated in serum-free pseudo-amniotic fluid produced very low levels of PGE2, even when arachidonic acid (1 microM) was present. Pretreatment of cells with dexamethasone (50 nM) for 21 h increased the PGE2 output 6- to 7-fold in 2-h incubations only in the presence of arachidonic acid. The RNA synthesis inhibitor, actinomycin D (1 microgram/ml), and the protein synthesis inhibitor, cycloheximide (40 micrograms/ml), each blocked dexamethasone-stimulated arachidonic acid conversion to PGE2. The time course of these events suggests that dexamethasone first initiates RNA synthesis. Acetylsalicylic acid, a specific and irreversible blocker of prostaglandin endoperoxide H synthase (cyclooxygenase), was used to determine whether dexamethasone could stimulate new enzyme synthesis. Cells treated first with acetylsalicylic acid (30 min) then dexamethasone (22 h) produced as much PGE2 in response to 1 microM arachidonate as did cells exposed to dexamethasone only. Exposing cells to acetylsalicylic acid after dexamethasone completely eliminated PGE2 output. These data suggest that dexamethasone stimulates the synthesis of prostaglandin endoperoxide H synthase.

Amnion↗

PubMed1988

Arachidonic acid incorporation into lipids of term human amnion.

There were no differences in the rate or amount of (1-14C)-labeled arachidonic acid incorporated into triacylglycerides, diacylglycerides, or any phospholipid species of freshly dispersed term human amnion cells obtained before or after labor. Both phosphatidylcholine and phosphatidylethanolamine incorporated 14C-arachidonic acid in proportion to their molar percent of total amnion phospholipids, but phosphatidylinositol incorporated three times as much 14C-arachidonic acid, suggesting either a rapid turnover in this specific phospholipid pool or a greater specificity for the transfer of arachidonoyl-coenzyme A to lysophosphatidylinositol. No or little competition of 14C-arachidonic acid incorporation into triacylglycerides or phospholipids occurred with palmitic acid, linoleic acid, or gamma-linolenic acid. However, dihomo-gamma-linolenic acid, eicosapentaenoic acid, and unlabeled arachidonic acid were effective inhibitors. We conclude that the term amnion has high acyl transferase activity, that no change in the basal activity of this enzyme occurs with the onset of labor, and that a specific acyl transferase exists for 20-carbon polyunsaturated fatty acids.

Amnion↗

PubMed1988

The action of epidermal growth factor on human amnion prostaglandin E2 output.

The mechanism of stimulatory action of epidermal growth factor on term human amnion prostaglandin E2 production was studied. Monolayer cultures of amnion epithelial cells from spontaneous vaginal deliveries were preincubated for 24 h with serum-free media and treated with epidermal growth factor, calcium ionophore A23187 (4.5 microM), and arachidonate. Cumulative prostaglandin E2 output was not stimulated by epidermal growth factor (less than or equal to 200 ng/mL) or A23187 alone or the two added together. Pretreating the cells with epidermal growth factor for at least 2 h followed by A23187 or arachidonate (in the continuing presence of epidermal growth factor), however, stimulated prostaglandin E2 output up to 14-fold. The maximum effect of epidermal growth factor was attained at 1-10 ng/mL, while the EC50 was 0.2-0.32 ng/mL. Ionophore- or arachidonate-promoted prostaglandin E2 output was not stimulated by pretreatment with platelet-derived growth factor, fibroblast growth factor, and beta-transforming growth factor. Cycloheximide added before, at the same time as, or up to 30-60 min after epidermal growth factor completely abolished the stimulation. Epidermal growth factor did not affect [14C]arachidonate incorporation into cells or cell lipids. These results suggest that epidermal growth factor promotes, specifically and in a protein synthesis dependent manner, the conversion of arachidonate to prostaglandin E2. The provision of exogenous or endogenously liberated arachidonate is also necessary for enhanced amnion prostaglandin E2 production.

Amnion↗

PubMed1988

Stimulation of human amnion prostaglandin E2 production by activators of protein kinase-C.

We tested the possibility that the activation of protein kinase-C by the tumor-promoter phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) or diacylglycerol stimulates the production of prostaglandin E2 (PGE2) by the amnion. Confluent primary cultures of human amnion epithelial cells were adapted to serum-free medium and treated with the agonists for up to 8 h. Cumulative PGE2 output in the medium was measured by RIA. TPA, a potent activator of protein kinase-C, stimulated basal PGE2 output from less than 50 pg/well.5 h to 3 ng/well.5 h (P less than 0.01) in a time- and dose-dependent manner. 4-Methoxy-TPA, a weak tumor promoter derivative of TPA, was ineffective when tested in the same concentration range as TPA (1 nmol/L to 1 mumol/L). Neither calcium ionophore A23187 (20 nmol/L) nor arachidonate (1 mumol/L) stimulated PGE2 output alone, but each agonist potentiated the effect of TPA as much as 5-fold (P less than 0.01). 1,2-Dioctanoyl-sn-glycerol stimulated PGE2 output 4- to 7-fold (P less than 0.05), and this effect was potentiated by Ca ionophore and arachidonate. Studies involving actinomycin-D and cycloheximide indicated that the stimulatory effect of TPA was dependent on RNA synthesis during the first 60 min and on protein synthesis during the entire length of the phorbol ester treatment period (300 min). TPA was also able to stimulate PGE2 production after irreversible inactivation of PG endoperoxide synthase activity with acetylsalicylic acid. These results suggest that activation of protein kinase-C in amnion cells increases the de novo synthesis of the PG endoperoxide synthase enzyme in a RNA synthesis-dependent manner. Elevated intracellular calcium levels contribute to the stimulation apparently by increasing the availability of endogenous arachidonate for subsequent conversion to PGE2.

Amnion↗

PubMed1988

Glucocorticoids stimulate prostaglandin synthesis in human amnion cells by a receptor-mediated mechanism.

Prostaglandin E2 (PGE2) synthesis by human amnion increases with the onset of labor and is thought to participate in the initiation and maintenance of parturition. Since cortisol levels increase in amniotic fluid in late pregnancy, we studied the effects of glucocorticoids on cultured term human amnion cell PGE2 output. In 24-h studies, the synthetic glucocorticoid dexamethasone stimulated basal PGE2 output 2-fold over control levels at 16-500 nmol/L. PGE2 output was dramatically stimulated (greater than 10-fold) when, after dexamethasone pretreatment, the cells were incubated with calcium ionophore A23187 or arachidonic acid (AA) for 2 h. Maximum effects were achieved at 31 nmol/L dexamethasone. Basal PGE2 output was stimulated at 12 h of dexamethasone treatment, whereas A23187- or AA-stimulated PGE2 output was enhanced after 3-6 h of dexamethasone pretreatment. Cortisol (50 and 500 nmol/L) also enhanced basal and stimulated PGE2 output, while dehydroepiandrosterone sulfate, 17 beta-estradiol, and progesterone were ineffective. The glucocorticoid receptor antagonist RU 38486 attenuated dexamethasone-enhanced basal and stimulated PGE2 output. Dexamethasone pretreatment had no effect on basal or stimulated PGE2 output from cultured term chorion cells, suggesting tissue specificity. We conclude that glucocorticoids specifically enhance PGE2 output from cultured amnion cells via a receptor-mediated mechanism. We speculate that the action of glucocorticoids is to increase the capacity of the cells to convert AA to PGE2.

Amnion↗

PubMed1988

Hydromyelia associated with arrested hydrocephalus.

A 16-year-old male with a 9-year history of spontaneously arrested hydrocephalus was noted to have hydrosyringomyelia and increased intracranial pressure shortly after sustaining minor head trauma. His symptoms resolved completely following ventriculoperitoneal shunt replacement. Hydrosyringomyelia may occur in the setting of long-standing, apparently arrested hydrocephalus.

Adolescent↗

PubMed1987

Effects of oxygen, calcium ionophore, and arachidonic acid on prostaglandin production by monolayer cultures of mixed cells and endothelial cells from rat fetal lungs.

Prostaglandins (PGs) synthesized by fetal and neonatal lungs play pivotal roles in pulmonary physiology, especially during the transition from uterine to independent life. One regulator of prostaglandin synthesis at this time may be oxygen. We examined the effects of 1% O2, 21% O2 and 50% O2 in 5% CO2, balance N2 (PO2 values in medium = 30 +/- 4, 142 +/- 4, and 260 +/- 3 mm Hg, respectively), on prostaglandin production from monolayer cultures of mixed or endothelial cells prepared from day 20 gestation rat fetal lungs. Cells were untreated or stimulated to produce prostaglandins by the addition of the calcium ionophore, A23187 (10(-5) M), or the prostaglandin precursor, arachidonic acid (AA, 1 microgram/ml). Prostaglandins 6-keto F1 alpha (6KF, the hydrolysis metabolite of prostacyclin, PGI2), E2, F2 alpha and 13,14-dihydro-15-keto PGF2 alpha (FM, the enzymatic metabolite of PGF2 alpha) were measured by radioimmunoassay. The basal release of 6KF from mixed cells into serum-free medium was approximately 2 ng/10(6) cells/3 days. The levels of 6KF were 10-fold greater than those of the other prostaglandins. Basal endothelial cell release of 6 KF was 30 ng/10(6) cells/3 days, and this was 15- to 100-fold greater than that of the other prostaglandins measured. In mixed cells, oxygen treatment for 3 days had no effect upon the basal release of any prostaglandin, nor was there any effect of oxygen upon the basal 6KF or PGE2 production in endothelial cells. However, both PGF2 alpha and PGFM production by endothelial cells was decreased (p less than 0.05) in 50% O2 compared to 1% O2. Both A23187 and AA enhanced prostaglandin release from mixed and endothelial cells. Ionophore-stimulated 6KF net production in mixed cells was greater in 21% O2 than in 1% O2 (p less than 0.05). Calcium ionophore stimulated the net production of 6KF and PGE2 in endothelial cells in 21% O2 versus 1% O2 (p less than 0.05), and AA enhanced the net production of 6KF, PGE2 and PGF2 alpha in endothelial cells in 21% O2 versus 1% O2. We conclude that rat fetal pulmonary cells produce prostaglandins from endogenous and exogenous substrates, that prostaglandin production is sensitive to Ca2+-mobilizing agents, and that the production of the vasodilators PGI2 and PGE2 increases in the presence of 21% O2 and a stimulating factor.

Animals↗

PubMed1987

Identification of calmodulin-like activity in term human amnion: effect of calmodulin inhibitors on prostaglandin biosynthesis.

Human amnion prostaglandin E2 (PGE2) synthesis increases with the onset of labour, and this synthesis is Ca2+-dependent. To understand better the mechanism of Ca2+-stimulated PGE2 biosynthesis, studies were performed to identify the presence of the intracellular Ca2+-mediator, calmodulin, in human amnion and to examine its role in PGE2 synthesis. Calmodulin-like activity was identified by the ability of the microsomal and cytosolic fractions of the 105,000g centrifugation of amnion homogenate to stimulate cyclic AMP-dependent phosphodiesterase activity. Cytosolic fractions consistently stimulated phosphodiesterase activity more than microsomal fractions (P less than 0.001) in paired samples from term human amnions. This activity was calcium-dependent. The cytosolic and microsomal factors increased the Vmax but not the Km of phosphodiesterase. There were no differences in these parameters with the onset of labour. The distribution of calmodulin-like activity between microsomes and cytosol was similar to the distribution of calmodulin mass as determined by radioimmunoassay. Three structurally different inhibitors of calmodulin activity, calmidazolium, trifluoperazine and W7, were tested for their ability to inhibit cytosolic factor-stimulated phosphodiesterase activity and to inhibit PGE2 output from dispersed amnion cells obtained before the onset of labour at term (cesarean section cells) or after spontaneous labour and vaginal delivery (spontaneous labour cells). The 50% inhibitory concentrations of the calmodulin antagonists in the phosphodiesterase assay were: trifluoperazine (6.7 microM), calmidazolium (0.11 microM), and W7 (24 microM). Trifluoperazine inhibited both basal and calcium ionophore (A23187)-stimulated PGE2 output from cesarean section cells and spontaneous labour amnion cells. Calmidazolium inhibited basal PGE2 output in cesarean section cells and spontaneous labour cells, but had no effect on A23187-stimulated output. W7 inhibited only the ionophore-stimulated PGE2 output in cesarean section amnion cells. The rank order of inhibition of both phosphodiesterase activation and basal PGE2 output was: calmidazolium greater than trifluoperazine greater than W7. These results suggest that human amnion contains calmodulin and that its distribution, concentration and activity remain unchanged with the onset of labour. The data suggest, although not conclusively, that calmodulin may, in part, play a role in amnion cell PGE2 production. Further investigation of calmodulin effects upon specific enzymes in the PGE2 synthetic pathway will be necessary to elucidate a role for calmodulin in PGE2 production.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1987

The relationship between fetal breathing movements and prostaglandin E2 during ACTH-induced labour in sheep.

We measured fetal breathing movements and fetal carotid arterial prostaglandin E concentrations during adrenocorticotrophin-induced labour in 6 pregnant sheep and in 6 control animals starting at day 127. The 6 ACTH-treated animals went into labour on average 97 h after the onset of infusion and the incidence of fetal breathing movements diminished during the last 12h before the onset of labour. There was a significant negative relationship between the incidence of fetal breathing movements and fetal carotid arterial prostaglandin E concentrations (r = -0.88; P less than 0.001) in ACTH treated animals. These data suggest a role for prostaglandin E in the diminution of fetal breathing movements prior to the onset of labour.

Adrenocorticotropic Hormone↗

PubMed1986

Development of receptors for leukotriene B4 on HL-60 cells induced to differentiate by 1 alpha,25-dihydroxyvitamin D3.

The incubation of HL-60 human promyelocytic leukemia cells for 7 days with 100 nM 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] induced differentiation into monocyte-like cells, as assessed by morphologic and biochemical characteristics. Stereospecific receptors for leukotriene B4 (LTB4) developed on the surface of the HL-60 cell-derived monocytes that had the capacity to transduce LTB4 stimulation of a transient increase in the cytosolic concentration of calcium ([Ca+2]in). HL-60 cell-derived monocytes, but not undifferentiated HL-60 cells, expressed a high affinity subset of 6400 +/- 3700 receptors per cell with a dissociation constant (Kd) of 2.3 +/- 1 nM (mean +/- SD, n = 3) and a low affinity subset of approximately 2.2 X 10(6) receptors per cell with an apparent Kd of 680 +/- 410 nM. Derivatives of LTB4 inhibited the binding of [3H]LTB4 to HL-60 cell-derived monocytes with a rank order of potency of LTB4 greater than 20-OH-LTB4 greater than 3-aminopropyl amide-LTB4, which is similar to the order for LTB4 receptors of human blood PMNL. In contrast, leukotrienes C4 and D4 and formyl-methionyl chemotactic peptides did not inhibit the binding of [3H] LTB4, which demonstrates the specificity of these receptors for isomers of 5,12-dihydroxy-eicosatetraenoic acid. LTB4 stimulated an increase in [Ca+2]in in HL-60 cell-derived monocytes which reached 50% of the maximal level at an LTB4 concentration of 0.5 nM (EC50). Preincubation of HL-60 cell-derived monocytes with 10 nM LTB4 resulted in a selective loss of high affinity receptors, as assessed by binding of [3H]LTB4, and a 200-fold increase in the EC50 for stimulation by LTB4 of increases in [Ca+2]in, without alterations in either the low affinity receptors for LTB4 or the responsiveness of [Ca+2]in to formyl-methionyl chemotactic peptides. HL-60 cells that are induced to differentiate into monocytes thus develop stereospecific receptors for LTB4 with binding and transductional characteristics similar to those of human blood PMNL.

Calcitriol↗

PubMed1986

Prostaglandin concentrations in peripheral plasma and ovarian and uterine plasma and tissue in relation to oviposition in hens.

An increase in the plasma concentrations of prostaglandins (PGs) is associated with uterine contractile activity and with oviposition in the hen. In order to assess the contribution of potential sources of prostaglandins to the increase in prostaglandin levels observed at oviposition, prostaglandins E2, F2 alpha, and 13,14-dihydro-15-keto PGF2 alpha (PGFM, the stable but biologically less active metabolite of PGF2 alpha) were measured in plasma from the brachial vein, ovarian follicular vein and uterine vein, and in tissues from ovarian follicles and the uterus 12 h before and at midsequence oviposition or a terminal oviposition. These two ovipositions differ in that a midsequence oviposition is followed within 0.25-1.0 h by the next ovulation of the sequence, whereas the terminal oviposition is followed by an ovulation 14 h later. The concentration of PGFM in plasma from the brachial vein increased at midsequence oviposition, while the levels of PGE2 were unchanged. Prostaglandin E2, F2 alpha, and FM levels were each similar in the plasma from the brachial and uterine veins at the time of midsequence oviposition. In plasma from the largest preovulatory follicle, the concentration of PGF2 alpha and PGFM increased 19- and 7-fold, respectively, from 12 h before midsequence oviposition to midsequence oviposition, although no changes were observed in the concentrations of PGE2 during this interval. The levels of PGF2 alpha increased in the tissues of the two largest preovulatory follicles and the two most recently ruptured follicles during the 12-h period before a midsequence oviposition, while there was no change or a decrease in PGE2 levels in these tissues during the same interval. In contrast, the concentration of PGF2 alpha did not increase during the 12-h period preceding the terminal oviposition of the sequence in plasma from the brachial, uterine, or follicular veins.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

The effect of indomethacin on ovarian prostaglandin release in hens.

Indomethacin, an inhibitor of prostaglandin (PG) synthetase, will block uterine muscle electromyographic activity (EMG activity) and oviposition at a midsequence oviposition and ovulation in domestic hens, but does not block the increase in EMG activity associated with the first ovulation of a sequence. To assess the potential relationship between prostaglandin release from the ovarian follicles and EMG activity in egg-laying hens, we determined the concentrations of PGF2 alpha, 13,14-dihydro-15-keto-PGF2 alpha (PGFM), and PGE2 in brachial, ovarian follicular and uterine venous plasma and tissues in relation to uterine muscle EMG activity at the first ovulation and at a midsequence oviposition. The concentrations were measured after an i.m. injection (25 mg/hen) of indomethacin. In control hens sampled hourly, beginning 4 h before the peak of EMG activity at the first ovulation of a sequence, there was a sharp increase (p less than 0.05) in concentrations of PGF2 alpha and PGFM in brachial vein plasma coincident with the increase (p less than 0.05) in uterine EMG activity. Hens pretreated with indomethacin also had increased plasma PGF2 alpha and PGFM levels (p less than 0.05) in brachial vein plasma and increased uterine EMG activity (p less than 0.05) at this time. Indomethacin treatment lowered but did not eliminate mean levels of PGF2 alpha in the venous effluent from the largest preovulatory follicle at the first ovulation (36.0 +/- 9.9 ng/ml vs. 14.4 +/- 1.8 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

Prostaglandin concentrations in ovine maternal and fetal tissues at late gestation.

Maternal and fetal sheep organs were measured for their concentrations of prostaglandins (PG) E2, F2 alpha, 13,14-dihydro-15-keto PGF2 alpha (PGFM), 6-keto PGF1 alpha (hydrolysis produce of PGI2), and 6-keto PGE1 (enzymatic product of PGI2) by radioimmunoassay at day 131 of pregnancy (0.90 gestation). It was observed that the concentrations of PGFM were greater (p less than 0.01) in maternal endometrium than in any other maternal tissue or any other PG measured in endometrium. The lowest concentrations of PG in maternal tissues were in the myometrium, while PGE2 and 6-keto PGF1 alpha were present in maternal lungs in high concentrations. Fetal prostaglandin concentrations were high in the chorioallantois, fetal portion of the cotyledons and amnion, while they were very low in the kidney, liver, and lung. Fetal lung concentrations were lower than maternal lung concentrations (p less than 0.01) for all PG measured. In fetal aorta and ductus arteriosus, 6-keto PGF1 alpha concentrations were significantly greater (p less than 0.05) than all other measured PG, while in umbilical artery and vein 6-keto PGF1 alpha levels were equal to PGE2 levels. 6-Keto PGE1 concentrations were consistently among the lowest in all tissues measured. These results suggest that the endometrium may serve as a metabolic barrier to PG diffusing from the chorioallantois to the myometrium, that the capacity of pulmonary tissue to produce PG may increase with age, that the fetal membranes and cotyledons may be one major source of circulating PG in the fetus, and that 6-keto PGF1 alpha is the major metabolite of PGI2 in ovine tissues.

6-Ketoprostaglandin F1 alpha↗