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 (PGs) participate in the inflammatory response, but the contribution of endogenously synthesized PGs to edema formation and increased vascular permeability is not known. Using a 10% scald burn in the rat, we measured water content (as percent, wet minus dry/wet weight) and 131I-RISA leakage (counts/g dry tissue) in scalded and normal skin at 30 minutes and 3 hr post injury. Four groups (10 rats/group) in each time period studied: control; scald; scald, 5 mg/kg indomethacin; scald, 10 mg/kg indomethacin. Indomethacin was administered intravenously 30 minutes before the scald; RISA was injected intravenously 30 min before termination of the study. In all indomethacin-treated groups immunoreactive plasma PGA was significantly lower (p less than 0.05) than in scalded, untreated groups. All scalded groups showed significantly higher RISA counts and water content than did the control group (p less than 0.01). At 30 min post-injury the indomethacin -treated groups did not differ from the untreated scald group (p greater than 0.20). In the 3 hour study all scalded groups had significantly higher content and RISA counts than control (p less than 0.01). Thus PGs produced during thermal trauma do not greatly contribute to the edema formation and increase in vascular permeability.
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PMID:Effect of inhibiting prostaglandin synthesis on edema formation and albumin leakage during thermal trauma in the rat. 50 95

The role of prostaglandins in blood pressure regulation was studied in normal rats and in animals with renal artery constriction. The effects of chronic inhibition of prostaglandin (PG) synthesis on arterial pressure were observed, and renal medullary PG synthesis was measured in vitro. The prostaglandin synthetase inhibitor indomethacin was given in a dose of 2 mg/kg/day by mouth to one of two groups of male Wistar rats with a unilateral renal artery constriction and the other kidney untouched, and to one of two sham-clipped groups. Systolic blood pressures were higher in indomethacin-treated clipped rats than in non-indomethacin-treated clipped animals, and at 18 days averaged 188 mm Hg (plus or minus SEM 5.9, n = 36) and 162 mm Hg (plus or minus SEM 7.6, n = 34), respectively (P less than 0.005 for data pooled from two experiments). Indomethacin did not affect pressures of sham-clipped animals treated for 40 days. Analysis of PG synthesis by gas-liquid chromatography in renal medullary slices incubated for 30 minutes in Krebs-Henseleit buffer showed: (1) 40% suppression of PGE synthesis in hypertensive animals (P less than 0.001): (2) no differences between clipped and untouched kidneys; (3) chronic indomethacin treatment did not affect PGE synthesis in the in vitro buffer system; and (4) no PGA synthesis was detected. In a further experiment in which medullary slices were incubated in plasma of rats treated with equivalent doses of indomethacin, PGE synthesis was suppressed by 35%. The experiments support the concept that prostaglandins modulate pressor mechanisms which come into play when renal blood flow is drastically reduced. The effects could be mediated by PG synthesis in the kidney and/or in other systemic vascular beds.
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PMID:Renal prostaglandin synthesis in the Goldblatt hypertensive rat. 113 85

A charcoal adsorption method was developed to measure specific prostaglandin binding in low speed supernates of hamster myometrial homogenates. This method was used to characterize and quantitate PGE-1-specific binding. The equilibrium binding constants and the concentration of specific PGE-1 binding sites were determined during the hamster estrous cycle. The apparent association constant for 12 different preparations was 1.16 plus or minus 0.08 times 10-9M-1. The concentration of PGE-1 specific binding sites was significantly higher on days 2 and 3 of the estrous cycle that it was on days 1 or 4. The competition for PGE-1 binding sites by PGE-2, PGF-2alpha, tpga-1 and various PGE-1 metabolites and derivatives was measured in hamster myometrial homogenates. Relative affinities of the natural prostaglandins for the PGE-1 binding sites, calculated by parallel line assay, were: PGE-2 greater than PGE-1 greater than PGA-1 greater than PGF-2alpha. For PGE-1 metabolites the relative affinities were: PGE-1 greater than 13,14-dihydro-PGE-1 greater than 13,14-dihydro-15-keto-PGE-1 greater than 15-keto-PGE-1. For the analogs and derivatives the compounds tested ranked as: 16,16-dimethyl-PGE-1 greater than PGE-1 methyl ester greater than 17-phenyl-18,19,20-trinor-PGE-1 greater than 15(S) 15-methyl-PGE-1 methyl ester. Arachidonic acid, bis-homo-gamma-linolenic acid and 7-oxa-13 prostynoic acid had relative affinities greater than 0.1 compared to PGE-1 equal 100. Indomethacin had a relative affinity of 0.4 compared to PGE-1.
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PMID:Prostaglandin specific binding in hamster myometrial low speed supernatant. 116

The role of cyclooxygenase and lipoxygenase metabolites of arachidonic acid in experimental esophageal were lumenally perfused for 1 h with acidified saline (pH 2.0) with or without pepsin followed by a second hour with acidified saline. Separate groups of pepsin-perfused animals were pretreated with indomethacin, a cyclooxygenase inhibitor, or BW755C, a lipoxygenase-cyclooxygenase inhibitor. Esophageal injury was graded grossly. H+ and hemoglobin fluxes were determined. Acidified saline caused no significant damage. Pepsin induced moderate injury. Indomethacin decreased pepsin-induced H+ flux by 55% without affecting the other indices. BW755C, by all measurements, dramatically increased pepsin-induced injury. In separate experiments, cyclooxygenase activity was decreased by indomethacin and BW755C by 62% and 49%, respectively. Lipoxygenase activity was decreased 74% by BW755C and was not significantly affected by indomethacin. These results suggest that esophageal cytoprotection is mediated by endogenous lipoxygenase metabolites.
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PMID:Role of arachidonic acid metabolites in acid-pepsin injury to rabbit esophagus. 250 Nov 39

The inhibitory action of 5-hydroxytryptamine (5-HT) on gastric function was studied in vagotomized rats. 5-HT (0.6, 1 or 5 mgkg-1, s.c.) dose-dependently reduced gastric acid secretion evoked by histamine, pentagastrin or methacholine. Pepsin secretion induced by pentagastrin or methacholine was also depressed by 5-HT. Basal secretion of both acid and pepsin was not significantly affected by any of the three 5-HT doses. Indomethacin pretreatment, which significantly decreased gastric mucosal prostaglandin E2 content, did not modify the inhibitory effects of 5-HT on histamine-induced acid secretion, nor did phentolamine or propranolol. This study suggests that 5-HT inhibits gastric secretory function through mechanisms other than by sympathetic influence or increased prostaglandin synthesis. The inhibitory action appears not to be vagus-dependent. Other mechanisms of action are discussed.
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PMID:The inhibitory action of 5-hydroxytryptamine on gastric secretory function in rats. 395 6

The relationship between prostaglandins (PG) and interferon (IFN) was investigated. IFN induced the synthesis of immunoreactive PGE and PGA at early and late stages, respectively, of vaccinia virus infection in mouse L fibroblasts. Only species-specific IFN possessed this activity and PG synthesis was stimulated in virus-infected cells, while normal L cells were not affected. The vaccinia virus infection did not significantly alter PG synthesis in the absence of IFN. Indomethacin increased the rate of vaccinia virus replication and partially inhibited the IFN-induced protection of L cells. The addition of exogenous PGA1 only partially reversed this effect. Finally, short-term PGA treatment induced the synthesis of two enzymes (protein kinase and 2,5A synthetase) thought to be partially responsible for the antiviral action of interferon. These findings suggest that a prostaglandin or PG-related compound seems to mediate at least one aspect of IFN action.
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PMID:The relationship between the antiviral action of interferon and prostaglandins in virus-infected murine cells. 619 67

Using the Fell technique of organ culture of 8-day chick embryo femoral and tibial rudiments, the effects of indomethacin, dihomo-gamma-linolenic acid and arachidonic acid on limb rudiment linear growth and differentiation were investigated. Indomethacin (50 and 100 mumol/l) elicited a statistically significant decrease in rudiment linear growth without affecting differentiation or cell structure. Dihomo-gamma-linolenic acid and arachidonic acid, both at 100 mumol/l, exerted no effect on limb rudiment linear growth or differentiation. From previous work, it has been shown that PGA1 and PGB1 caused a marked inhibition of linear growth, PGA1 being cytotoxic. The failure of the prostaglandin (PG) precursors to reproduce these effects suggests that PGA or PGB biosynthesis in embryonic chondrocytes plays no significant role in cartilage growth regulatory mechanisms. Moreover, the growth inhibitory effect of the PG cyclooxygenase inhibitor, indomethacin, suggests that a product of arachidonic acid metabolism via the cyclooxygenase pathway may promote cartilage growth.
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PMID:Effects of prostanoid precursors and indomethacin on chick embryonic cartilage growth in organ culture. 640 86

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%.
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PMID:The prostaglandins of articular cartilage. I. Correlates of prostaglandin activity in a chondrocyte culture system. 720 51

The role of transforming growth factor alpha (TGFalpha) and prostaglandins (PGs) in the preferential growth of preneoplastic liver cells was studied. Rats received the genotoxic hepatocarcinogen N-nitrosomorpholine (NNM); placental glutathione S-transferase (GSTp) was used as a marker to identify preneoplastic foci. Preneoplastic foci expressing TGFalpha (TGFalpha(+)) grew more rapidly than TGFalpha negative (TGFalpha(-)) ones. Almost all tumours studied were positive for TGFalpha. The key enzymes of prostaglandin synthesis, cyclooxygenase I (Cox-1) and II (Cox-2), were present in all unaltered and preneoplastic cells and tended to decrease in the later stages of hepatocarcinogenesis. Immunostaining revealed that cultures of hepatocytes, isolated from NNM-treated livers by collagenase perfusion, contained 1-2% GSTp-positive (GSTp(+)) and 9% TGFalpha(+) hepatocytes; 0.6% of the cells were GSTp(+)/TGFalpha(+). Cox-1 and Cox-2 were present in all cells. DNA replication was almost exclusively associated with expression of TGFalpha. GSTp(+) hepatocytes showed a 3- to 4-fold higher probability of TGFalpha expression and of DNA synthesis than GSTp-negative (GSTp(-)) cells. PGE(2) or PGF(2alpha) increased expression of TGFalpha and DNA replication in GSTp(-) cells but not in GSTp(+) cells. PGA(2) and PGJ(2) decreased DNA synthesis in TGFalpha(+) cells without an obvious effect on the intracellular levels of TGFalpha. The Cox-2 inhibitor SC236 suppressed DNA replication preferentially in GSTp(+) cells; this inhibition was reversed by PGE(2)/F(2alpha). Indomethacin had no effect. These results suggest the following conclusions. (i) Growth regulation of preneoplastic GSTp(+) cells in culture exhibits distinct differences from GSTp(-) cells and elevated expression of TGFalpha contributes to their growth advantage. (ii) TGFalpha renders preneoplastic hepatocytes sensitive to suppression of DNA synthesis by PGA(2)/J(2). (iii) SC236, a Cox-2 inhibitor, may have preventive value in hepatocarcinogenesis.
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PMID:Role of transforming growth factor alpha and prostaglandins in preferential growth of preneoplastic rat hepatocytes. 1147 Jul 56