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)

The property of the neuronal membrane to be permeable to metabolic modifiers of two regulatory enzymes has been utilized to manipulate the spike activity of inspiratory (I) and expiratory-inspiratory (EI) neurons of the bulbar respiratory centre. The neurons have been classified according to their response to lung distention or collapse (alpha- or beta-type) and to hyperventilation (tonic firing denoted by "+", cessation of activity by "-"). Using extracellular microelectrodes for single unit recording, the medulla oblongata was superfused with a metabolite-containing CSF. The various neuronal sub-types exhibited a differential activating or inhibitory response to one or several metabolic effectors. For example Ialpha+ units were activated by 5 mM glucose-6-phosphatase (G-6-P) and 3.5 mM 3-phosphoglycerate (3-PGA), which both inhibited Ibeta+ neurons, while 5 mM AMP inhibited Ialpha+ much more strongly than Ibeta+ cells. The spike density of Ialpha- and Ibeta- neurons was increased in the presence of 2.5 mM fructose-6-phosphate and 3.5--5 mM AMP, but became reduced by G-6-P. In contrast, 3 mM fructose-1,6-diphosphate and 5 mM 3-PGA activated the Ialpha- but inhibited the Ibeta- neurons. The EIbeta units were characteristically activated by 10 mM citrate, which inhibited all I-type neurons. Activations of the Ialpha and Ibeta neurons led to an accelerated respiratory rate and a higher tidal volume, while the opposite was true for EIbeta neurons. Intravenous injection of metabolites could not duplicate the striking effects under local applications.
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PMID:Metabolic control of respiratory neuronal activity and the accompanying changes in breathing movements of the rabbit. 1. Mainpulation of inspiratory and expiratory-inspiratory neurons. 18 80

The effects of prostaglandin (PG) E1, E2, A1, F1alpha, F2alpha or D2 on the rat renal cortical, outer medullary and inner medullary adenylate cyclase-cyclic AMP systems were examined. While high concentrations (8X10-4M) of each prostaglandin stimulated adenylate cyclase activity in each area of the kidney, PGE1 was the only prostaglandin to stimulate at 10-7M. PGA's were the only prostaglandins tested besides PGE's which stimulated adenylate cyclase at less than 10-4M. This effect of PGA's was limited to the outer medulla. PGD2 was the least stimulatory. Observations with renal slices yielded qualitatively similar results. The PGE's were the most potent in each area with PGA's only stimulatory in the outer medulla. O2 deprivation (5% O2) lowered the slice cyclic AMP content in each area of the kidney. In the cortex and outer medulla, prostaglandin mediated increases in cyclic AMP content were either lower or absent at 5% O2 compared to 95% O2. However, in the inner medulla PGE stimulation was observed only at 5% O2 and not 95% O2. No other prostaglandins were found to increase inner medullary cyclic AMP content at 95% or 5% O2. These results illustrate that the adenylate cyclase-cyclic AMP system responds uniquely to prostaglandins in each area of the kidney. Consideration of these results along with correlative observations suggests that inner medullary produced PGE's may act as local modulators of inner medullary adenylate cyclase.
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PMID:Effects of prostaglandins on rat renal adenylate cyclase-cyclic AMP systems. 19 51

Prostaglandins (PG) have been shown to raise the level of cyclic AMP (cAMP) in various tissues, and to increase permeability. Whether both events are linked, is at present a matter of speculation. We have investigated the effects of PGE1, E2, A1, A2, F1alpha and F2alpha on an isolated rat mesentery placed in a diffusion cell (surface area : 2 sq.cm). The PGs (5 microgram/ml) increased the passage of (I 125) - Albumin across the mesentery. In other experiments, diks of rat mesentery (surface area : 2 sq.cm) have been incubated in assay tubes, and cAMP levels measured by a binding protein assay. We have observed an excellent correlation between increases in permeability and cAMP levels (r=0.961). In order of increasing potency on both parameters, the PGs may be classified as follows : PGF, PGA and PGE. In the rat mesentery, under the influence of prostaglandins, increases in permeability and in cAMP levels are apparently connected.
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PMID:The role of various prostaglandins on the correlation between permeability to albumin and cAMP levels in the isolated mesentery. 21 45

Avian erythrocytes export cyclic AMP by a means that prostaglandins A1 and A2, but not other eicosanoids, inhibit (EC50 approximately 45 nM). Several insect pheromones and the fatty acyl components of common membrane phospholipids also inhibit cyclic AMP efflux (EC50 approximately 30 microM). The presence of at least one double bond in the acyl chain enhances the effect. Unlike PGA, fatty acids probably do not act via formation of a glutathione adduct but very likely by altering membrane fluidity. Inhibition of cyclic AMP export provides a mechanism by which products of phospholipid metabolism can influence the cyclic AMP signaling pathway.
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PMID:Inhibition of cyclic AMP efflux by insect pheromones and fatty acids. 253 47

Effects of prostaglandins on the incorporation of [4,5-(3)H]leucine into growth hormone and its subsequent release into the incubation medium were studied. Incubation of rat anterior pituitary glands with 10(-6) M prostaglandin PGE(1) in tissue culture medium 199 for 7 hr caused a 40-300% increase in the release of labeled growth hormone into the incubation medium. PGE(1) at 10(-8) M increased growth hormone synthesis but not release. At 10(-6) M, PGE(2) had effects similar to PGE(1); PGA(1) increased growth hormone synthesis but not release. PGF(2alpha) was without effect on either synthesis or release of growth hormone.Prolactin synthesis and release were not affected by prostaglandins. All of the prostaglandins, at 10(-4) M, increased adenyl cyclase activity in the pituitary gland but phosphodiesterase activity was unaltered. Dibutyryl cyclic AMP, with or without caffeine, caused an up to 300% increase in labeled growth hormone release. No consistent effect of prolactin was observed. If potassium concentration was increased 10-fold, a 215% increase in growth hormone release was observed. A combination of hypertonic potassium and 10(-6) M PGE(1) increased growth hormone release 325%, suggesting that potassium and prostaglandins act by independent mechanisms. Addition of theophylline to pituitary gland, incubated in vitro, increased both the synthesis and release of growth hormone. Although fluoride greatly stimulated growth hormone release, it completely inhibited the incorporation of leucine into the hormone. Similarly, puromycin inhibited synthesis of growth hormone but did not block release induced by prostaglandin, dibutyryl cyclic AMP, theophylline, or fluoride. Prostaglandins increase pituitary adenyl cyclase activity and, presumably via cyclic AMP, increase growth hormone release, independently of protein synthesis.
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PMID:Release of pituitary growth hormone by prostaglandins and dibutyryl adenosine cyclic 3':5'-monophosphate in the absence of protein synthesis. 432 Sep 73

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 prostaglandin (PG) content of mitogen- and antigen-stimulated leukocyte cultures was examined by a radioimmunoassay procedure empolying an antiserum reactive with PGB(1) and PGB(2), the alkaline dehydration products of PGE and PGA. At 48 h, mitogen-activated mouse spleen cell cultures showed 2-10-fold increases in the PGE, but not in the PGA, component of immunoreactive PG (iPG) fractionated by silicic acid column chromatography. Increases in iPG were detectable by h 16 in spleen cell cultures incubated with staphylococcal enterotoxin B. Since iPG levels rose only in the culture supernates and not in cells exposed to mitogens for 48 h, increases reflected extracellular release of PG. The validity of the radioimmunoassay determinations of PGE in spleen cell cultures was supported by the results of concomitant assessment of the PGE(2) content of basal and enterotoxin-stimulated cultures by gas chromatography/mass spectrometry. By the latter method, the PGE(2) content was three-fold higher in enterotoxin-activated, compared to basal, cultures at 48 h. Aspirin effectively suppressed increases in both iPG and PGE(2). In spleen cell cultures prepared from mice previously inoculated with an attenuated strain of yellow fever virus in vivo and then incubated with this virus in vitro, iPG levels increased twofold over basal at 48 h. By contrast, iPG content of spleen cell cultures prepared from saline-inoculated mice was not appreciably altered by exposure to the virus in vitro. The enhancement of iPG release from cultured spleen cells by mitogens did not correlate with an ability of these agents to increase cellular cyclic AMP (cAMP) levels. Moreover, epinephrine and cholera toxin markedly increased spleen cell cAMP content but had no demonstrable effect on basal iPG levels, suggesting iPG release from these cells was not mediated by cAMP. Incubation with mitogens also enhanced the iPG content of 72-cultures of human peripheral leukocytes and of human lymphocytes isolated by nylon chromatography. However, the iPG of cultures of human lymphocytes purified by glass bead chromatography and of mouse thymocytes was not appreciably altered when these cells were cultured with mitogens, even though DNA synthesis in both instances was markedly increased. Accordingly, iPG release was not an invariable concomitant of increased DNA synthesis in lymphoid cell cultures. In summary, the results demonstrate that mitogen and antigen stimulation of leukocytes in culture may be accompanied by enhanced release of PGE. The mechanisms mediating this phenomenon and its biologic significance remain to be delineated, but participation of PGE in immunologically induced inflammatory responses seems possible.
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PMID:Release of prostaglandin by mitogen- and antigen-stimulated leukocytes in culture. 436 90

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 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


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