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 characteristics of the effects of catecholamines, prostaglandins, and adenosine on the adenosine 3',5'-monophosphate (cAMP) content of human astrocytoma cells are described. Catecholamines interact with a typical beta-adrenergic receptor, i.e., the order of potency of catecholamines is isoproterenol larger than or equal to epinephrine greater than norepinephrine greater than dopamine, and propranolol is an inhibitor but phentolamine is not. The prostaglandins interact with a receptor that recognized PGE-1, PGE-2, and PGA-1 but not PGF-2-alpha. The effects of PGE-1 are blocked by 7-oxa-13-prostynoic acid, indomethacin, and meclofenamic acid in a rapid, reversible manner. The cells contain another adenylate cyclase-linked receptor that recognizes adenosine and the adenine nucleotides but not guanosine, deoxyadenosine, or adenine. Theophylline and other methylxanthines are competitive inhibitors of the effect of adenosine. Each class of effector appears to stimulate adenylate cyclase by interacting with a structure-specific receptor. This follows from the observation that the effect of each class of agonists can be blocked selectively by the various inhibitors and is consistant with the observation that co-addition of different agonists results in additive effects on accumulation of cAMP. The magnitude of the effect of any of the classes of agonists can be influenced by a variety of factors, some of which may be related to the peculiarities of growth in culture: (1) The cells secrete cAMP into the medium, and the magnitude of this secretion for a given rise in intracellular cAMP is different for different agonists. (2) The exposure of the cells to catecholamines or prostaglandins leads to a loss of responsiveness to a subsequent challenge by the same agonist. The magnitude of the agonist-induced loss of responsiveness is dependent on the concentration of the agonist and the time of exposure. The process is at least partially agonist specific in that exposure of cells to isoproterenol can lead to greater than 90% loss in catecholamine responsiveness with less than 20% loss in responsiveness to prostaglandins. (3) The responsiveness of the cells also changes as a function of the age of the culture and as a function of cell density. (4) Finally, it can be demonstrated that cells maintained in culture for prolonged periods (months to years) may lose responsiveness to specific agonists while responsiveness to other agonists remains unchanges or actually increases. The advantages and disadvantages of the use of cells in culture for studies of the regulation of cAMP metabolism are discussed.
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PMID:Factors influencing the effect of hormones on the accumulation of cyclic AMP in cultured human astrocytoma cells. 16 56

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

A peptide-containing extract (PE) from Helix nervous system modifies the endogenous bursting pattern of electrical activity in Helix neurone F-1. This effect is similar to that induced in neuron F-1 by certain phosphodiesterase inhibitors and cAMP derivatives. The PE, and the vertebrate peptide hormones vasopressin and oxytocin, also cause an accumulation of cAMP in Helix ganglia in vitro. The factor in the PE which causes the cAMP accumulation is destroyed by Pronase, is lost on dialysis, and is stable to boiling. In all these respects it is identical to the factor which causes the change in neuronal electrical activity. The PE also stimulates adenylate cyclase activity in a crude membrane fraction prepared from Helix ganglion homogenates. This stimulation is abolished by prior dialysis of the PE, or pretreatment of the PE with pepsin, but is not affected by boiling of the PE. Pepsin-treated PE has no effect on electrical activity in neuron F-1. The adenylate cyclase-stimulating activity of the PE, like the factor which modifies neurone F-1 electrical activity, elutes in the void volume of a Sephadex G-10 column. The included volume of this column contains a factor which inhibits PE modification of neuronal electrical activity, and also inhibits both basal and PE-stimulated adenylate cyclase activity. The data are consistent with the possibility that cAMP mediates the effects of the PE on electrical activity in molluscan neurones.
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PMID:Modulation of electrical activity and cyclic nucleotide metabolism in molluscan nervous system by a peptide-containing nervous system extract. 20 Mar 7

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

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
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PMID:Pepsinogens: physiology, pharmacology pathophysiology and exercise. 1067 78