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)

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

This study was undertaken to see whether any changes in the concentration of seminal PGs (Prostaglandins) occurred following vasectomy when the testes are no longer in continuity with the lower genital tract. Samples of seminal fluid from males undergoing vasectomy were obtained on the day of operation, and 12 and 16 weeks after the operation. The samples were stored at -15 degrees Celsius and all analyses were carried out within 1 week of receipt. Prostaglandin content was analyzed by means of thin-layer chromatography and spectrophotometry. There was a significant rise in the level of all prostaglandins measured 12 weeks after the operation. At 16 weeks postvasectomy, both PGEs and PGAs were at a significantly higher level than before the operation, but the 190H PGAs were not. Only 1 man did not show any change in PGE concentration over the 16-week period, although marked changes were observed in his PGA level and 190H PGAs. 2 men exhibited lower seminal PGE levels after vasectomy and little change was observed in the level of other prostaglandins measured in 1 of these 2 men. All sperm counts fell to zero 12 weeks after vasectomy. The study shows that prostaglandins do not rise, even in part, as a secretion from the testis.
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PMID:Vasectomy and seminal prostaglandins. 468 1

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

Three prostaglandins (PGE(2), PGF(2alpha) and PGA(2)) are present in rabbit kidney medulla. An acidic lipid extract (0.165g) obtained from 2kg of frozen rabbit kidney cortex was separated by silicic acid chromatography to yield eluates containing fatty acids, possible non-polar prostaglandin metabolites, PGA, PGE and PGF compounds. Ultraviolet spectra of the eluates before and after treatment with sodium hydroxide did not yield chromophores typical of any known prostaglandins or related metabolites. By using more sensitive bioassay procedures (contraction of rabbit duodenum) weak activity equivalent to 60mug of PGE(2) and 10mug of PGF(2alpha) was detected in the PGE and PGF eluates respectively. Extraction and bioassay of fresh kidney cortex revealed no prostaglandin-like activity. Attempts to biosynthesize prostaglandins in fresh homogenates of rabbit kidney cortex from endogenous precursors and from added arachidonic acid were unsuccessful. When freshly prepared homogenates of rabbit kidney cortex were incubated with added PGE(1) no evidence of enzymic breakdown was obtained. It is concluded that rabbit kidney prostaglandins are present predominantly in the medulla and there are no cortical mechanisms for their biosynthesis or inactivation under normal conditions.
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PMID:Distribution of prostaglandins in rabbit kidney. 543 88

1. Prostaglandins A(1), E(1), F(1alpha) and F(2alpha) were infused into the vertebral artery of the chloralose-anaesthetized greyhound and the resulting cardiovascular responses were compared with those obtained on intravenous and intracarotid infusions in the same dose range.2. Infusions of PGF(2alpha) intravertebrally (4-64 (ng/kg)/min) caused an increase of blood pressure, tachycardia and a fall of central venous pressure. Cardiac output was increased and peripheral resistance was essentially unchanged. There was never any response to intravenous or intracarotid PGF(2alpha) infusions in this dose range.3. PGF(1alpha) was found to have similar effects to PGF(2alpha) but it was much less potent.4. PGE(1) infusions (4-360 (ng/kg)/min) into the vertebral artery caused a tachycardia which was greater than that obtained with intracarotid or intravenous infusions, but there was no significant effect on blood pressure.5. Infusions of PGA(1) caused a small fall of blood pressure accompanied by an increase of heart rate and the dose response relationships were similar for all three routes of administration.6. It is concluded that some prostaglandins can activate cardioregulatory centres within the territory of distribution of the vertebral artery. Prostaglandin F(2alpha) is the most potent of these.
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PMID:Cardiovascular effects of prostaglandins mediated by the central nervous system of the dog. 547 2

Antibodies to prostaglandin were obtained by immunization of rabbits with PGA(1), PGA(2), and PGE(1), protein conjugates of prostaglandins. The antibodies demonstrated specificity toward both the cyclopentane ring and the aliphatic side chains. With the use of these antibodies a highly sensitive radio-immunoassay capable of measuring less than picomolar amounts of PGA1, PGA2, and PGE1 has been developed.
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PMID:Radioimmunoassay for prostaglandins. 553 3

The ultraviolet (UV) and optical rotatory dispersion (ORD) spectra of prostaglandins E(1), A(1), B(1), and their naturally derived 15-epimers are presented. The dehydration sequence E --> A --> B under acidic and basic conditions has been studied by UV and ORD. Conditions for quantitative conversion of PGE(1) to PGA(1) are described. The combination of ORD and UV affords a nondestructive assay which can determine the relative amounts of E-, A-, and B-type prostaglandins with as little as 1-2 micro g of material. The total quantity of prostaglandins can be estimated (+/-15%) in this way or, more accurately, by treatment with alkali of an aliquot (200 ng is sufficient) and determination of the change in absorbance at 278 nm.
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PMID:Dehydration of prostaglandins: study by spectroscopic method. 578 3


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