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)

Testicular interstitial cells were utilized to study the effects of prostaglandins (PG) on in vitro testosterone production and to examine the role of cyclic adenosine-3',5'-monophosphate (cAMP) in this process. Testosterone production was assessed after 3 hour incubations while cAMP accumulation was examined after a 0.5 hour incubation period. Testosterone and cAMP were measured by radioimmunoassay. None of the PGs tested (PGA, PGA2, PGB1, PGE1, PGE2, PGF1alpha PGF2alpha) altered basal testosterone production when present in incubates at concentrations of 1.3 X 10(-8) M to 1.3 X 10(-4). However, at concentrations of 1.3 X 10(-4) M all of these PGs were capable of decreasing Luteinizing Hormone (LH; 100ng)-induced testosterone production. The inhibition of LH-induced testosterone production by the B, E and F series PGs was less pronounced than that for the A series. PGA1 and PGA2 exhibited 80% and 95% inhibition, respectively, at 1.3 X 10(4) M. The inhibitory action of 4 X 10(5) M PGA1 or PGA2 was evident within 30 minutes. Preincubation of interstitial cells with indomethacin (10(-5) or 10(-6) M) for 30 minutes did not alter subsequent basal or LH (100ng)-induced testosterone production. Accumulation of cAMP was stimulated by LH (10 microgram) or by PGs (1.3 X 10(-4) M PGA1, PGA2, PGB1, PGE1 or PGF2alpha). The PG-induced cAMP accumulation thus occurred at concentrations where LH-stimulated testosterone production was inhibited. Furthermore, PGA1 and PGA2 (1.3 X 10(-4) M) inhibited testosterone production induced by either 3-isobutyl-1-methyl xanthine (MIX; 10(-4) M or 10(-3) M) or dibutyryl cAMP (dbcAMP; 10(-4) M or 10(-3) M). These results indicate that PGs can block testosterone production by a direct effect on testicular interstitial cells and suggest that PGs exert their inhibitory action distal to stimulation of cAMP formation. PGs do not appear to play a role in the mechanism of LH action.
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PMID:Prostaglandin inhibition of testosterone production induced by luteinizing hormone, dibutyryl cyclic AMP or 3-isobutyl-1-methyl xanthine in dispersed rat testicular interstitial cells. 8 81

These studies were directed toward determining effects of selected vasoactive compounds on oxygenated erythrocytes. Considering the major circulatory effects that small changes in blood flow might initiate in sickle cell anemia patients, erythrocytes from individuals with this disease and from one person with the trait condition were included. PGA1, PGE1, and PGE2 significantly increase filtration times in normal erythrocytes (AA-type hemoglobin) at 10(-11) M by this method. From studies of the effects of L-epinephrine, D,L-isoproterenol, PGA1, PGA2, PGE1, PGE2, PGF1alpha and PGF2alpha on red blood cell filterabilities, the following observations and conclusions appear to hold: (1) Erythrocytes from different individuals (or from the same individual at different times) vary greatly in responses to these compounds. Effects of vasoactive compounds upon red cell filterability may be positive, negligible or negative. Decreased filterability (positive effect) was seen more frequently than increased. (2) Effects are observed with all compounds on some erythrocyte preparation at every concentration tested (10(-5), 10(-7), 10(-9), 10(-11) M). (3) Where epinephrine showed significant positive effect, PGA2 and PGE2 did also when tested. The reverse was not always true. (4) For PGA and PGE analogs, the subscript 2 analogs affected filterability more frequently. (5) When significant average effects for a group of donors were produced by a given compound at a particular concentration, these effects were positive for the donors studied.
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PMID:Examination of the filterability of oxygenated erythrocytes (containing normal, trait or sickle cell disease type hemoglobins) in the presence of L-epinephrine, D,L-isoproterenol or prostaglandins (PG) A1, A2, E1, E2, F1alpha or F2alpha. 84 33

The effects of PGA1, PGA2 and PGB1 on the vasculature of the liver and small intestine were studied in 73 dogs. Infusions were made into a branch of the superior mesenteric artery, the hepatic artery, portal vein or femoral vein. They decreased systemic arterial pressure and dilated the hepatic arterial and prehepatic splanchnic (small intestinal) vascular beds, PGA being most active. Dilator response was not decreased by beta-adrenergic blockade. Compounds appear to be inactivated by liver and decreased systemic pressure less when infused directly into liver circulation. Dilator response was transient, particulary in small intestine, and abated or even converted to constriction when infusion was continued for a period of time. Intrahepatic portal venous vasculature appeared to be constricted by PGA.
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PMID:Splanchnic vascular responses to the infusion of prostaglandins A1, A2 and B1. 95 18

The renal prostaglandins PGS2 and PGE2 possess potent antihypertensive and vasodepressor activity. The mechanism of blood pressure lowering effect is through peripheral arteriolar dilation with a fall in total peripheral resistance. PGA unlike PGE escape degradation by the lung and thus could circulate as antihypertensive hormones. Since plasma PGA levels rise in humans on a low sodium intake, it has been postulated that the beneficial effects of a low sodium diet in some hypertensives may be the result of an increase in peripheral vasodilating PGA. Support that plasma PGA may be a regulator of systemic blood pressure is also derived from the fact a PGA-secreting renal tumor was associated with a fall in blood pressure and a rise in plasma PGA in a previously hypertensive woman. The removal of the tumor resulted in a return of blood pressure to elevated levels and a concomitant fall in PGA. Recently, a number of human patients with essential hypertension have been infused with PGA1 and PGA2. It was observed that there was an initial increase in renal blood flow, sodium and water excretion which was associated with no change in the elevated blood pressure. When blood pressure ultimately fell, there was a return of renal blood flow, sodium and water excretion to preinfusion levels. It would appear that PGA compounds act as 'ideal' antihypertensive agents since they favorably effect renal resistance, sodium and water homeostasis, plasma volume, total peripheral resistance, blood pressure and indirectly cardiac output through baroreceptor stimulation, all factors known to be important in etiology in human hypertension.
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PMID:Renal prostaglandins. 110 Oct 92

A specific, sensitive and accurate radioimmunoassay (RIA) method for the measurement of prostaglandin A1 (PGA1) in either human whole blood or plasma is described. Whole blood is immediately lysed with distilled water containing tritiated indicator. When plasma is assayed, the blood samples are handled at 4 C and rapidly centrifuged. The lysate or plasma is adjusted to pH 5 with buffer and quickly extracted with 5% methanol in dichloromethane. The whole blood or plasma extract is then purified by Sephadex LH20 chromatography using the system methanol: methylene chloride (5:95) which separates the major groups of PGA, PGE and PGF. The RIA is then performed using an antiserum generated in rabbits from PGA1 coupled to bovine thyroglobulin. The antibody is highly specific, possessing very low cross reactivity to other prostaglandins (PGA2, PGE, PGB and PGF). Activated florisil or ammonium sulfate can be used to separate bound from free prostaglandin. This whole blood or plasma method yields blank values of only 2 +/- 2 pg per sample with a between assay precision determined by duplicate analysis of 8% and interassay precision of 3%. The mean whole blood PGA1 concentration in 27 subjects in 2.5 +/- 1.6 (SD) ng per 100 ml. No significant sex difference in PGA1 levels was noted and values were similar whether measured in whole blood or cooled plasma rapidly prepared and extracted. These values of PGA1 are much lower than those RIA values reported by others for "PGA" using antibodies with lower specificities.
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PMID:A radioimmunoassay for prostaglandin A1 in human peripheral blood. 115 43

The effects of intrarenal infusion of prostaglandins (PGs) of the E, A and F series on renal vascular resistance and on vasoconstrictor responses to renal nerve stimulation (RNS), norepinephrine (NE) and angiotensin (A) were determined in the in situ feline kidney under conditions of controlled blood flow. Infusion of PGE2 (3 and 0.3 mug/min) and PGE1 (3 mug/min) resulted in a marked decrease in renal perfusion pressure and a reduction in responses to all vasoconstrictor stimuli. PGE2 (0.03 mug/min) did not alter perfusion pressure. However, responses to RNS and A but not to NE were attenuated. PGA2 (3 and 0.3 mug/min) had no significant effect on perfusion pressure. PGA1 (3 mug/min) resulted in a transient decrease in renal vascular resistance which was not maintained during the infusion period. PGA2 (3 mug/min) reduced the response to RNS at 10 and 30 cps and reduced the response to A, whereas responses to NE were not affected. PGA2 (0.3 mug/min) had no effect on responses to either of the pressor stimuli. PGA1 infusion resulted in an enhanced response to RNS at the highest stimulus frequency and decreased the response elicited by A. PGF2alpha (3 mug/min) had no significant effect on renal vascular resistance or on responses to NE and nerve stimulation. However, the response to angiotensin was decreased and responses to RNS at 10 and 30 cps were decreased 30 minutes after the PGF2alpha infusion. The present data demonstrate that, of the natural renal PGs, PGE2 and PGA2 possess the capacity to modulate the effects of the sympathetic nervous system on the feline kidney. In addition, the effects of PGE and PGA on responses to adrenergic stimuli and on vascular resistance could be separated.
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PMID:Influence of prostaglandins E, A and F on vasoconstrictor responses to norepinephrine, renal nerve stimulation and angiotensin in the feline kidney. 124 15

The effects of prostaglandins (PGs) A and J, which are anti-tumor eicosanoids, on the proliferation of cultured vascular smooth muscle cells were investigated. Serum-stimulated DNA synthesis was potently inhibited by PGA1, PGA2, PGJ2, and delta 12-PGJ2 in similar dose-dependent fashions. The effects of PGA1 and PGA2 were reversible when they were removed from the culture media, whereas recoveries were only partial in the cells treated with PGJ2 and delta 12-PGJ2. PGs were effective even if they were added immediately before entry into S phase. Inhibition of DNA synthesis was sustained when hydroxyurea, which blocks cell cycle at the G1/S border, was added after the removal of PGA2, and vice versa; PGs blocked DNA synthesis when they were added after the removal of hydroxyurea. Levels of c-myc mRNA formed two peaks during the G1 phase, at 1-2 h and at 8-12 h. The PGs did not affect the first elevation, but enhanced the second and sustained it up to 18-24 h, whereas in controls, c-myc mRNA decreased quickly after entry into S phase. The rate of degradation of c-myc mRNA was much smaller in PG-treated cells than in nontreated cells. We conclude, therefore, that PGA and PGJ inhibit a crucial event(s) in the cell cycle occurring at the G1/S border, but that this inhibition is not accompanied by the reduction in c-myc gene expression in contrast with some types of tumor cells treated with PGs.
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PMID:Prostaglandins A and J arrest the cell cycle of cultured vascular smooth muscle cells without suppression of c-myc expression. 157 2

Liver fatty acid binding protein (L-FABP) is the principal target protein of the hepatic carcinogen N-(2-fluorenyl)acetamide (2-acetylaminofluorene) in rat liver. In addition, the cyclopentenone prostaglandins (PG), PGA, PGJ2, and delta 12-PGJ2, inhibit the growth of many cell types in vitro. This report describes the preferential binding of the growth inhibitory prostaglandins by L-FABP and the reversible inhibition of thymidine incorporation into DNA by PGA2 and delta 12-PGJ2 in primary cultures of purified rat hepatocytes. As a model ligand, [3H]PGA1 bound to L-FABP specifically, reversibly, rapidly, and with high affinity. Its dissociation constants were 134 nM (high affinity) and 3.6 microM (low affinity). The high-affinity binding of [3H]PGA1 was 9- and approximately 13-fold more avid than the binding of the conventional fatty acid ligands, oleic acid and arachidonic acid, respectively. The abilities of different prostaglandins to compete with the high-affinity binding of [3H]PGA1 correlated with their growth inhibitory activities reported previously and here. The growth inhibitory cyclopentenone prostaglandins (PGA1, PGA2, delta 12-PGJ2, and PGJ2) were the best competitive ligands, intermediate competitors were the weak growth inhibitors PGE1 and PGD2, and the poorest competitors were PGE2 and PGF2 alpha, which stimulate rather than inhibit DNA synthesis in rat hepatocytes in primary culture. The in vitro actions of L-FABP are compatible with those of a specific and dissociable carrier of growth inhibitory prostaglandins in rat hepatocytes and suggest that the carcinogen may usurp the cellular machinery of the growth inhibitory prostaglandins.
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PMID:Preferential binding of growth inhibitory prostaglandins by the target protein of a carcinogen. 225 Dec 82

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)
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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

We have previously shown that prostaglandins of the A series potently inhibit virus replication in several virus-host systems in vitro. In the present report we have studied the effect of a long-acting synthetic analog of PGA, 16,16-dimethyl-PGA2(Di-M-PGA2), on virus infection in vivo, using as a model Balb/c mice infected with influenza A (PR8) virus. Depending upon the dose of viral inoculum, PR8 virus caused the death of 50 to 100% of the animals in a period of 8-20 days. Di-M-PGA2-treatment significantly increased mouse survival by an average of 40%, independently of the dose of inoculum and the age of the animals. The fact that Di-M-PGA2-treatment decreased virus titers in the lungs and did not alter the host immune response, suggested that PGA's therapeutic action was due to suppression of virus replication. Finally, two anti-inflammatory compounds, which inhibit prostaglandin synthesis, aspirin and indomethacin, were shown not to significantly alter mouse survival in this system.
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PMID:Antiviral activity of a synthetic analog of prostaglandin A in mice infected with influenza A virus. 335 75


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