Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00790 (PGA)
 2,475 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Prostaglandins were injected into the third ventricle of unanaesthetized cats and rabbits whilst rectal temperature was recorded.2. In cats prostaglandin E(1) and E(2) (PGE(1) and PGE(2)) produced hyperthermia which mostly began within a minute of injection and lasted 1 or more hours. With PGE(1) the hyperthermia was shown to be dose dependent between 10 ng and 10 mug (2.8 x 10(-11) and 2.8 x 10(-8)M). The hyperthermia was associated with vigorous shivering, skin vasoconstriction and piloerection. In several experiments a secondary rise in temperature occurred a few hours after the injection but such an effect was sometimes observed with control injections of 0.9% NaCl solution as well.3. None of the other prostaglandins (A(1), F(1alpha), F(2alpha)) examined in cats had an immediate or strong effect on temperature comparable to the hyperthermia produced by PGE(1) and PGE(2).4. In rabbits PGE(1) (2 mug) also caused hyperthermia which began shortly after the injection and lasted for hours. PGF(2alpha) and PGA(1), did not affect temperature.5. In cats it was seen that an intraperitoneal injection of 4-acetamidophenol (paracetamol 50 mg/kg) did not affect the initial strong hyperthermia produced by PGE(1) and PGE(2) but abolished the secondary rise.6. The possibility is discussed that PGE(1) plays a role as a central transmitter or modulator in temperature regulation.
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PMID:Effects on body temperature of prostaglandins of the A, E and F series on injection into the third ventricle of unanaesthetized cats and rabbits. 433 Sep 29

Incubation of L-929 and L-2071 fibroblasts with prostaglandin E(1) (PGE(1)) caused a rapid increase in the cyclic AMP content of these cells. A maximal effect was produced with 0.2 mug PGE(1) per ml. At a concentration of 4 mug/ml, PGE(2) was almost equally effective, but PGF(2alpha) and PGA(2) were much less so. 2.6 muM epinephrine, 0.4 mM serotonin, and 0.2% ethanol were without effect. In L-929 cells, cyclic AMP concentrations remained elevated for 2-5 hr, and then declined, although even after a 24-hr incubation the medium contained PGE(1) in a concentration sufficient to increase maximally the cyclic AMP content of cells not previously exposed to this compound. A second addition of PGE(1) after 5 or 24 hr did not produce another increase in the concentration of cyclic AMP. After incubation with PGE(1) for 24 hr, cyclic AMP phosphodiesterase activity, assayed with 0.56 muM substrate, was increased 30-100%; the activity rose further between 24 and 48 hr. It is suggested that the increase in phosphodiesterase activity that appears to be a consequence of prolonged elevation of cyclic AMP concentration may account at least in part for the apparent "refractoriness" to PGE(1) that develops after incubation for several hours with this compound.
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PMID:Prostaglandin E 1 effects on adenosine 3':5'-cyclic monophosphate concentration and phosphodiesterase activity in fibroblasts (mouse L cells-tissue culture-enzyme kinetics-prostaglandin homologues). 433 44

Prostaglandins E(1) and E(2) significantly stimulated the synthesis of aldosterone, corticosterone, and to a lesser degree, cortisol in the outer slices of beef adrenal tissue. PGA, PGF(1a), and PGF(2a) were ineffective.PGE(1) was found to stimulate steroidogenesis in a manner similar to that of adrenocorticotropin (ACTH) in (a) needing calcium, (b) being inhibited by puromycin but not actinomycin D, (c) increasing the levels of cyclic AMP, and (d) not having an additive effect to exogenous cyclic AMP. PGE(1) did not produce an additive effect with either submaximal or maximal amounts of ACTH but did have an additive effect with angiotensin. These results are in keeping with the hypothesis that PGE(1) shares a receptor site on the plasma membrane with ACTH.
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PMID:Adrenocortical steroidogenesis: the effects of prostaglandins. 434 27

The effects of agents that elevate intracellular cyclic adenosine 3',5'-monophosphate (cAMP) have been studied with respect to phagocytosis by guinea pig polymorphonuclear leukocytes. The investigation depends upon the use of a precise method for following ingestion. Theophylline, dibutyryl cAMP, and prostaglandins inhibited the phagocytosis of starch particles. The inhibitions caused by prostaglandins E(1), E(2), and F(2alpha) (PGE(1), PGE(2), and PGF(2alpha)) were synergistic with that due to theophylline. Inhibition by PGA(1) and PGA(2) was not. At equal concentrations the order of increasing inhibition of phagocytosis (assayed at 10 min) by the prostaglandins was PGE(1) < PGF(2alpha) < PGE(2) < PGA(1) = PGA(2). Our results are consistent with the hypothesis that increased intracellular levels of cAMP impair the phagocyte's ability to ingest particles. The mechanism of the inhibition has not been defined. The increment in oxidation of [1-(14)C]glucose to (14)CO(2) that normally accompanies phagocytosis was found to be depressed in the presence of PGE(1) or theophylline, together or individually as expected from the inhibition of phagocytosis. Paradoxically, oxygen consumption although depressed by theophylline or PGE(1) plus theophylline, was stimulated by PGE(1) alone.
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PMID:The depression of phagocytosis by exogenous cyclic nucleotides, prostaglandins, and theophylline. 437 83

By use of two novel techniques for detecting extremely small amounts of PGs, studies were conducted elucidating the mechanism of urate crystal-induced inflammation. Rats deficient in EFA and thus deficient in PGs received injections of monosodium urate crystals into the footpad. The EFA-deficient animals developed less swelling than did normal animals. However, when a 1-ng dose of PGE-1, PGE-2, PGA-2, or PGF-2-alpha was added along with the urate injection the swelling was enhanced to approximately normal levels. In the second technique the swelling induced by injection of two different urate crystals was compared. Urate crystals heated to 200 degrees C produced less swelling in normal rats than did similar urate crystals heated only to 50 degrees C. However when a 1-ng dose of PGE-1, PGE-2 or PGF-2-alpha was added to the heated urate crystals injection the swelling increased to approximately the swelling in normal controls receiving urate heated to 50 degrees C. Comments are presented suggesting that urate crystal inflammation may be a membrane disease.
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PMID:Effect of prostaglandins in urate crystal inflammation. 445 26

Prostaglandins are analogs of the parent 20 carbon prostanoic acid. They are divided into 4 series: PGE; PGF; PGA; PGB, according to the presence of functionalities in the cyclopentane structure. Biosynthesis of prostaglandins were first independently reported by Bergstrom et.al. and van Dorp et.al. who showed that certain w-6-unsaturated fatty acids were biological precursors of prostaglandins. Later, various investigators reported the biosynthesis of prostaglandins of the different series. The 2 most widely used routes of prostaglandins synthesis are 1) the Corey cyclopentyl-lactone route, and 2) the bicyclohexane route. The synthesis is divided into 1) naturally occuring primary prostaglandins and 2) the prostaglandin analogs and derived prostaglandins. Because of the general instability of natural prostaglandins in the basic and acidic milieu, various preparations of prostaglandins and chemically stable dosage forms have been developed. Various methods used in analyzing prostaglandins include: 1) TLC; 2) GLC; 3) spectral methods; 4) radioimmunoassay; and 5) enzymatic assay. In vitro and in vivo studies on the metabolism and catabolism of various prostaglandins showed that they are rapidly metabolized in various animal systems and humans. The major routes for this metabolic transformation are: 1) oxidation of the secondary C15 hydroxy group; 2) reduction of the C13 double bond; 3) B-oxidation; 4) w-hydroxylation; and 5) w-oxidation. Prostaglandins produce a wide range of biological effects on animal and human systems (the reproductive; gastrointestinal; respiratory; and cardiovascular systems). The biological actions of prostaglandins on animal and human reproductive tissue vary depending on the particular prostaglandin studied and hormonal state of the tissue. Certain prostaglandins can decrease the tonus, frequency, and amplitude of spontaneous contractions of human uterine strips while other prostaglandins can cause contraction of isolated myometrial strips. Prostaglandins are widely used in labor induction; induction of therapeutic abortion; and fertility control. Prostaglandins have also been found to either increase or decrease cyclic AMP; inhibit ADP-induced platelet aggregation; lower blood pressure in animals; affect lipid and carbohydrate metabolism, and prevent adjuvant arthritis.
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PMID:Prostaglandins. 456 72

The details of a radioimmunoassay capable of measuring as 5 pg of prostaglandin A, E, and F (PGA, PGE, and PGF) in human and rat plasma are described. Plasma samples are extracted (with 4000 cpm [(3)H] PGE(1) added for calculation of recovery) with an organic solvent system at an apparent pH of 5.8 and then chromatographed on silicic acid columns with increasing concentrations of methanol to separate PGA, PGE, and PGF. Each chromatographed sample is measured by radioimmunoassay, using the homologous antibody and tritiated marker. 40 normal individuals had mean plasma concentrations of PGA, PGE, and PGF of 1062+/-107 pg/ml, 385+/-30 pg/ml, and 141+/-15 pg/ml, respectively. Elevated PGE levels were measured in the plasma of patients with medullary carcinoma of the thyroid, carcinoid, and neuroblastoma. Treatment of rats with indomethacin decreased serum PGE levels by 67%. The radioimmunoassay appears to be of considerable experimental as well as clinical interest.
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PMID:Radioimmunoassay measurement of prostaglandins E, A, and F in human plasma. 468 79

The procedures which may be and are being used to provide a basis for the analysis of submicrogram quantitities of prostaglandins are surveyed. Discussion is focused on the following: 1) sources of standards; 2) properties (effect of different pH values, effect of blood, metabolism, solubility); 3) extraction; 4) detection; 5) estimation (ultraviolet, optical rotatory dispersion, densitometry, radioimmunoassay, enzymatic assay, isotopic methods, bioassay); 6) separation of prostaglandins (separation of PGE, PGF, and PGA with PGB compounds, separation of PGA and PGB compounds, and separation of individual prostaglandins); and 6) structural identification. Methods of prostaglandin analysis, with the required sensitivity for application to individual tissue and fluid specimens, are still in the developmental state. Although prostaglandins may be ubiquitous throughout the animal kingdom, no systematic study of their distribution has been made to date. Recent work has shown that PGE1 has a potent effect on the formation of 3',5' cyclic adenosine monophosphate (cyclic AMP) which is widely believed to be an intracellular intermediate in hormone action.
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PMID:Separation, identification, and estimation of prostaglandins. 489 63

1. The relationship between the chemical structure and the direct vasoactivity of different prostaglandins administered intra-arterially was studied in the dog hindlimb preparation.2. All of the prostaglandins studied, except PGF(1alpha) and PGF(2alpha), caused a dose related decrease in the femoral arterial perfusion pressure in dogs in which the femoral arterial blood flow was kept constant, indicating the direct vasodilator action of these prostaglandins.3. Among the prostaglandins studied, PGE(1) is the most potent vasodilator. Comparing the chemical structure and vasodilator action of PGE(1) with those of different prostaglandins, the following conclusions can be made:4. The formation of the Delta(5) double bond in PGE(1) causes no change in its vasodilator activity, whereas the saturation of the Delta(13) double bond of PGE(1) slightly reduces its activity.5. The alterations in the orientation and length of the carboxyl and alkyl side chains reduce markedly the vasodilator action of PGE- and PGA-compounds.6. The presence of a carbonyl group at C9 is the most important requirement for the potent vasodilator action of PGE(1). On the other hand, the presence and S-configuration of a hydroxyl group at C15 are essential for the intrinsic action at the receptor sites in the vascular smooth muscle, but may not be responsible for the vasodilator action.7. The esterification of PGE(1) or PGE(2) and a triple bond formation and the replacement of C7 with oxygen in prostaglandin appear to reduce or abolish their vasodilator action.
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PMID:Relationship between the chemical structure of prostaglandins and their vasoactivities in dogs. 501 41

1. Slices or bits of rabbit tissues, not exceeding 100 mg, were incubated in tissue culture medium containing tritium-labelled prostaglandin ([(3)H]PG). In some experiments, incubation medium also contained saturating concentrations of an unlabelled prostaglandin (PG), or [(14)C]-sucrose for determination of extracellular space. At the end of the incubation period, usually 1 hr, the tissues were removed and weighed, and their (3)H (and (14)C) content were determined along with that of a unit volume of medium.2. Tissues known to play a central role in PG metabolism (lung and liver) and in its excretion (kidney cortex) and tissues which have a known function in blood-brain and blood-ocular barriers (choroid plexuses and ciliary processes) show a large accumulation of (3)H when incubated in a medium containing [(3)H]PGE(1). In addition, tissues of the female reproductive tract, and the aorta of the rabbit show similar (3)H accumulation. When uncorrected for tissue solid content or extracellular water volume, the extent of this accumulation is two- to sixfold. Calculated on the basis that all excess (3)H is present in the free form in the intracellular water, the accumulation ratio for ciliary processes, for example, indicates an over fortysix-fold gradient of PGE(1) across the cell membrane.3. Tissues which accumulate [(3)H]PGE(1) also accumulate [(3)H]PGA(1), [(3)H]PGF(1alpha) and [(3)H]PGF(2alpha). In some tissues specificity is, however, apparent; in the lung accumulation of [(3)H]PGA(1) was significantly greater than that of [(3)H]PGF(1alpha).4. The extent of [(3)H]PGE(1) accumulation was decreased, or in some tissues completely inhibited, by incubation at 2 degrees C, or by addition of large concentrations of unlabelled PG.5. Accumulation of [(3)H]PGE(1) by the foetal liver is not apparent on the 20th day of gestation, but is fully developed by the 30th day of gestation. The foetal lung does not accumulate [(3)H]PGE(1) at any stage of gestation.6. In some tissues, most notably muscle, there appears to be full equilibrium of [(3)H]PGE(1) between tissue water and medium within 1 hr of incubation.7. PGs are partially excluded from the intracellular volume of some other tissues, most notably the spleen and subcutaneous connective tissues. This apparent exclusion cannot be blocked by incubation in the cold, or by the addition of saturating levels of unlabelled PG.8. The simplest explanation for all observed results is that cell membranes are, in general, impermeable to PGs. However, there are specific, carrier-mediated mechanisms across some membranes which facilitate the entry of PGs. In some cells these transport mechanisms are linked to a source of metabolic energy, and/or to the counter-transport of some other substance, thus allowing net accumulation of PGs against a concentration gradient. Alternatively, (3)H accumulation may represent adsorption of [(3)H]PGs or one of their labelled metabolites on to specific adsorption sites.
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PMID:Accumulation and apparent active transport of prostaglandins by some rabbit tissues in vitro. 502 Sep 82


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