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

Since their discovery more than 40 years ago, PGs have been shown to be present in many tissues. The 10 members of this family (PGA-PGI and TxA) that have been identified to date have been noted to have a wide variety of pharmacologic actions. Frequently, the actions of one PG are in direct opposition to those of another. This has led to the theory that PGs play an important role in maintaining homeostasis in many organ systems. Evidence accumulated indicates a major role for PGs in the regulation of blood pressure, the autonomic nervous system, blood flow and platelet aggregation. This is in addition to specific actions on other tissues such as the CNS and reproductive system. A summary of PG actions in humans is contained in Table 1. Unfortunately, the PGs have not been as useful therapeutically as originally hoped. Currently, they are being used to induce labor and to maintain the patency of the PDA. However, they still hold much promise and with the development of synthetic analogues and specific synthesis inhibitors, they should live up to this promise in the future.
 ...
PMID:Prostaglandins: an overview. 74 49

A luteotropic role for prostaglandins (PGs) during the luteal phase of the menstrual cycle of rhesus monkeys was suggested by the observation that intraluteal infusion of a PG synthesis inhibitor caused premature luteolysis. This study was designed to identify PGs that promote luteal function in primates. First, the effects of various PGs on progesterone (P) production by macaque luteal cells were examined in vitro. Collagenase-dispersed luteal cells from midluteal phase of the menstrual cycle (Day 6-7 after the estimated surge of LH, n = 3) were incubated with 0-5,000 ng/ml PGE2, PGD, 6 beta PGI1 (a stable analogue of PGI2), PGA2, or PGF2 alpha alone or with hCG (100 ng/ml). PGE2, PGD2, and 6 beta PGI1 alone stimulated (p less than 0.05) P production to a similar extent (2- to 3-fold over basal) as hCG alone, whereas PGA2 and PGF2 alpha alone had no effect on P production. Stimulation (p less than 0.05) of P synthesis by PGE2, PGD2, and 6 beta PGI1 in combination with hCG was similar to that of hCG alone. Whereas PGA2 inhibited gonadotropin-induced P production (p less than 0.05), that in the presence of PGF2 alpha plus hCG tended (p = 0.05) to remain elevated. Second, the effects of various PGs on P production during chronic infusion into the CL were studied in vivo. Saline with or without 0.1% BSA (n = 12), PGE2 (300 ng/h; n = 4), PGD2 (300 ng/h; n = 4), 6 beta PGI1 (500 ng/h; n = 3), PGA2 (300 ng/h; n = 4), or PGF2 alpha (10 ng/h; n = 8) was infused via osmotic minipump beginning at midluteal phase (Days 5-8 after the estimated LH surge) until menses. In addition, the same dose of PGE, PGD, PGI, or PGA was infused in combination with PGF2 alpha (n = 3-4/group) for 7 days. P levels over 5 days preceding treatment were not different among groups. In 5 of 8 monkeys receiving PGF2 alpha alone, P declined to less than 0.5 ng/ml within 72 h after initiation of infusion and was lower (p less than 0.05) than controls. The length of the luteal phase in PGF2 alpha-infused monkeys was shortened (12.3 +/- 0.9 days; mean +/- SEM, n = 8; p less than 0.05) compared to controls (15.8 +/- 0.5). Intraluteal infusion of PGE, PGD, PGI, or PGA alone did not affect patterns of circulating P or luteal phase length.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Intraluteal infusions of prostaglandins of the E, D, I, and A series prevent PGF2 alpha-induced, but not spontaneous, luteal regression in rhesus monkeys. 227 32

Total human pepsinogen (PG) was isolated from gastric fundic mucosa and PGA (formerly called PGI) from urine, using standard ion-exchange and gel filtration techniques. Gastric PGA was separated from PGC (formerly called PGII) either by immunoaffinity or high resolution ion-exchange chromatography (fast protein liquid chromatography, Pharmacia, Uppsala, Sweden). The individual PGA isozymogens 2, 3, 4 and 5 could be isolated to homogeneity with the aid of the same ion-exchanger. Evidence was obtained for the existence of secondary modifications of the PGA fractions 3, 4 and 5, electrophoretically overlapping the primary (genetic) isozymogens.
 ...
PMID:Purification of the pepsinogen A isozymogens by means of high resolution ion-exchange chromatography. Evidence for post-translational modifications. 407 Sep 62

Following close intra-arterial administration to the carotid and femoral arterial beds of the anaesthetised dog the rank order of potency for producing vasodilation was PGE greater than 11-deoxy PGE0 greater than PGA greater than PGI2 greater than PGB with the 1- and 2-series prostaglandins equipotent. PGI2 was about 60 times weaker than PGE1. In the mesenteric arterial bed the rank order of potency for producing vasodilation was the same except PGI2 was about equipotent with PGE1. The absolute potency of the prostaglandins, with the exception of PGI, was similar on all three vascular beds. A similar differential action of PGI2 relative to PGE1 was also observed following both left intraventricular and intravenous administration. We suggest that all three arterial beds contain PGE-receptors mediating vasodilatation at which the E-series prostaglandins are potent and PGI2 is weak. In addition the mesenteric bed contains PGI2-receptors which are absent or sparse in the carotid and femoral beds.
 ...
PMID:Comparison of the potencies of some prostaglandins as vasodilators in three vascular beds of the anaesthetised dog. 674 31

Suspensions of aggregated chondrocytes display active prostaglandin (PG) production. Radioimmunoassay of culture media and thin layer chromatographic analysis suggests that PGE2 is the primary PG synthesized. In order of decreasing concentration, the following PG were tentatively identified; PGE greater than PGI greater than PGA + PGB greater than or equal to PGF1+2 greater than TxB. An inverse logarithmic relationship was identified between PG synthesis and cells cultured at densities of 1.5 to 7.5 x 10(6) cells/ml. Little or no change in the PG distribution profile was seen at these high cell densities. Maximum PG synthesis was attained after 36 hours of incubation with persistence of high synthetic levels up to 48 hours. PGE2 production measured at various post-isolation intervals indicated an initial high rate of synthesis during the first 4 hours which decreased with time up to 24 hours. Cartilage explant organ cultures demonstrated a similar level of PG synthesis suggesting minimal effect of matrix on cellular PG production. Indomethacin (5 microgram/ml) inhibited PG synthesis by 70% within 4 hours and 85% after 24 hours of exposure. Arachidonic acid supplementation (10 microM) stimulated PG synthesis by 300%.
 ...
PMID:The prostaglandins of articular cartilage. I. Correlates of prostaglandin activity in a chondrocyte culture system. 720 51

Human gastric mucosa contains aspartic proteinases that can be separated electrophoretically on the basis of their physical properties into two major groups: Pepsinogen I (PGA, PGI); and Pepsinogen II (PGC, PGII). Pepsinogens consist of a single polypeptide chain with molecular weight of approximately 42,000 Da. Pepsinogens are mainly synthesized and secreted by the gastric chief cells of the human stomach before being converted into the proteolytic enzyme pepsin, which is crucial for the digestive processes in the stomach. Pepsinogen synthesis and secretion are regulated by positive and negative feed-back mechanisms. In the resting state pepsinogens are stored in granules, which inhibit further synthesis. After appropriate physiological or external chemical stimuli, pepsinogens are secreted in the stomach lumen where hydrochloric acid, secreted by the parietal cells, converts them into the corresponding active enzyme pepsins. The stimulus-secreting coupling mechanisms of pepsinogens appear to include at least two major pathways: one involving cAMP as a mediator, the other involving modification of intracellular Ca(2+)concentration. Physiological or external chemical stimuli acting through the intracellular metabolic adenyl cyclase are more effective in inducing ' de novo ' pepsinogen synthesis than those acting through intracellular Ca(2+). The activation of protein kinase C (PK-C) would appear to be involved in regulatory processes. The measurement of pepsinogens A and C in the serum is considered to be one of the non-invasive biochemical markers for monitoring peptic secretion and obtaining information on the gastric mucosa status of healthy subjects. Recently, pepsinogen measurements have been used as an effective biochemical method for evaluating and monitoring patients with gastrointestinal diseases and for checking the effects of drug treatment. The level of PGA in the serum is always high in normal gastritis, while in atrophic gastritis it is always low. In both cases the PGC level in the serum is high. In most gastrointestinal pathologies the ratio between the PGA/PGC decreases. Various reports concerning hormone and/or enzyme modification as well as gastrointestinal distress in the case of long distance exercise have been reported. It has been suggested that the origin of the gastrointestinal distress experienced by long distance runners is a transient ischaemia of the gastric mucosa; it is also suggested that a hypobaric-hypoxic environment could contribute to induce gastric mucosa necrosis. Interrelation between gastrointestinal distress, hypobaric-hypoxic environment and modifications of PGA and PGC, gastrin and cortisol was evaluated in 13 athletes after a marathon performed at 4300 m. Gastrointestinal symptoms occurred in approximately 40% of the athletes. After the race the athletes showed a significant increase of gastrin and cortisol, while the ratio between PGA/PGC decreased. No relationship was observed between gastrointestinal symptoms and hormonal changes after the race. A control group of five subjects, who had been exposed to the same environmental conditions, showed no gastrointestinal or hormonal alteration. Conversely, control subjects presented a significant decrease of cortisol related to the circadian rhythm. The same incidence of gastrointestinal symptoms at high altitude and at sea level and the absence of pathological alteration of PGA and PGC in the serum of the athletes indicates that running a marathon and living for 6 days at 4300 m does not induce gastric mucosa necrosis. Cortisol and gastrin alteration observed in the athletes at this altitude would seem to be related to an activation of the mesopontine and forebrain structures involved in the behavioural and metabolic integration of the autonomic control and arousal and psychophysical-exercise stress. 2000 Academic Press@p$hr
 ...
PMID:Pepsinogens: physiology, pharmacology pathophysiology and exercise. 1067 78

High concentrations of PGE(2) and PGF(2alpha) were identified by radio-immunoassay (RIA) and/or gas chromatography/mass spectrometry (GC/MS) in the hemolymph, salivary glands and saliva of the lone star tick Amblyomma americanum (L.). Binding studies indicated that PGE(2) was free and not bound to any proteins in the hemolymph. A small amount of 6-keto-PGF(1alpha) (breakdown product of PGI(2); prostacyclin) was also found in the salivary glands but not in the hemolymph or saliva. Neither PGD(2) nor PGA(2)/B(2) was detected in any tick material investigated. Although PGE(2) was found in the gut contents, only small amounts of label crossed the gut into the hemolymph during artificial feeding with labeled PGE(2), indicating that the high amounts of PGE(2) in hemolymph and salivary glands are not sequestered from the host blood meal. Isolated salivary glands and salivary gland homogenates demonstrated robust synthesis of PGE(2) at high concentrations of exogenous arachidonic acid. Synthesis by the salivary glands was monitored by measuring increasing PGE(2) with increasing arachidonic acid by RIA, GC/MS and labeled PGE(2) in the presence of labeled arachidonic acid. Synthesis was inhibited in a dose-dependent manner by indomethacin indicating that the cyclooxygenase synthesizing prostaglandins in ticks shares similarities to the enzyme found in mammals.
 ...
PMID:Identity and synthesis of prostaglandins in the lone star tick, Amblyomma americanum (L.), as assessed by radio-immunoassay and gas chromatography/mass spectrometry. 1180 5

The interaction between fungal endopolygalacturonases (EPGs) and polygalacturonase-inhibiting proteins (PGIPs) found in plant cell walls has been well established. The typical EPG/PGIP interaction is characterized by high affinity, reversibility, and a 1:1 stoichiometry that results in lowering the catalytic rate of a particular endopolygalacturonase by up to 99.7%. Various EPG and PGIP isoforms and glycoforms have been isolated and characterized, and combinations of EPGs and PGIPs demonstrate a range of enzyme inhibition. EPG/PGIP interactions have prompted many researchers to suspect the involvement of these proteins in the production of specific signals (oligosaccharins) during plant pathogenesis. We have recently reported on initial studies in our laboratory indicating that, for certain EPG/PGIP combinations, the specific activity of EPG is increased beyond that characteristic of the enzyme alone. In this paper, we present a detailed analysis of the product of the interaction of native Phaseolus vulgaris PGIP-2 with five EPGs from Aspergillus niger, namely PGI, PGII, PGA, PGB, and PGC in the presence of homogalacturonan. We demonstrate that for PGA and PGC, the interaction with PGIP-2 may result in either inhibition or activation in a manner that is pH dependent. This data suggests the need for a reevaluation of the conventional description applied to PGIPs; suggestions include polygalacturonase-binding protein and polygalacturonase-modulating protein.
 ...
PMID:Polygalacturonase-inhibiting proteins can function as activators of polygalacturonase. 1530 10

Efficient RIA procedures are required for determination of prostaglandins (PGF(2alpha), PGE(2), PGI(2) and their metabolites) in bovine blood plasma to elucidate their significance in reproductive endocrinology. A new rapid efficient prepurification was developed using commercial octadecyl silicagel cartridges. Prepurification is especially necessary for the determination of 13,14-dihydro-15-keto-PGE(2) (PGEM). After prepurification, PGEM was first converted into the more stable 13,14-dihydro-15-keto-PGA(2) (PGAM) and measured in a RIA-system for PGAM. For PGF(2alpha), 13,14-dihydro-15-keto-PGF(2alpha) (PGFM), PGE(2) and 6-keto-PGF(1alpha) direct tests using 50 mul plasma per tube were elaborated. The validity of the tests was monitored by high performance liquid chromatography radioimmunoassay (HPLC RIA ). Infusion studies using PGF(2alpha) and PGE(2) showed that about 10% of these hormones remained unmetabolized after the first passage through the lungs. The biological half life of the metabolites PGFM and PGEM in bovines was estimated to be 4 min. Thus, PGFM and PGEM measurements in the peripheral circulation reflect even short-term secretory changes of PGF(2alpha) and PGE(2). During the infusion of PGF(2alpha) the levels of progesterone decreased but were not affected by PGE(2). Both prostaglandins caused increased oxytocin secretion. In the cow peripartum first PGEM elevations were measured 5 to 8 d ante partum, whereas PGFM increased 1 to 2 d ante partum. Then both prostaglandins increased simultaneously until parturition. In the postpartal phase PGFM was higher than PGEM, and both prostaglandins remained elevated for several days. Prostacyclin levels remained unchanged during the peripartal period.
 ...
PMID:Improvement of radioimmunoassays for prostaglandins in bovine blood plasma and their application to monitor reproductive functions. 1672 87

Maternal diabetes significantly increases the risk of congenital malformations, and the mechanisms involved are not yet clarified. This study was designed to address peroxisome proliferator-activated receptor delta (PPARdelta) involvement in diabetic embryopathy. We investigated the concentrations of PPARdelta and its endogenous agonist prostaglandin (PG)I(2), as well as the effect of PPARdelta activation on lipid metabolism and PGE(2) concentrations in embryos from control and streptozotocin-induced diabetic rats during early organogenesis. Embryos from diabetic rats showed decreased concentrations of PPARdelta and its endogenous agonist PGI(2) when compared with controls. In embryos from control rats, the addition of the PPARdelta activators (cPGI(2) and PGA(1)) increased embryonic phospholipid levels and de novo phospholipid synthesis studied using (14)C-acetate as a tracer. PGE(2) formed from arachidonate released from phospholipid stores was also up-regulated by PPARdelta activators. In embryos from diabetic rats, reduced phospholipid synthesis and PGE(2) content were observed, and clearly up-regulated by cPGI(2) additions to values similar to those found in control embryos. These data suggest that PPARdelta may play an important role in lipid metabolic and signalling pathways during embryo organogenesis, developmental pathways that are altered in embryos from diabetic rats, possibly as a result of a reduction in levels of PPARdelta and its endogenous activator PGI(2).
 ...
PMID:PPARdelta and its activator PGI2 are reduced in diabetic embryopathy: involvement of PPARdelta activation in lipid metabolic and signalling pathways in rat embryo early organogenesis. 1714 78


1 2 Next >>