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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Studies were made of the effects on responses to vasoconstrictor agents of prostaglandins released from Krebs perfused isolated kidneys of genetic hypertensive and normotensive rats. 2. Prostaglandin E-like activity, detected by bioassay, was released from kidneys of both groups of rats during the vasoconstriction produced by noradrenaline, angiotensin or prostaglandin F2alpha. 3. In preparations obtained from hypertensive rats, responses to higher doses of noradrenaline or angiotensin were initially greater than those from normotensive rats and these were then reduced to a greater extent by infusion of indomethacin, which abolished release of prostaglandin E-like activity. Thereafter, in kidneys of either group, vasoconstriction to noradrenaline was potentiated by infusion of prostaglandin E2. 4. We conclude that, in rats, renal prostaglandins released in response to vasoconstrictor agents could augment the effect of such agents and in genetic hypertensive rats release of renal prostaglandins could contribute to the disease.
Clin Sci Mol Med Suppl 1976 Dec
PMID:Contribution of prostaglandins to the renal vascular supersensitivity to vasoconstrictor agents exhibited by New Zealand genetic hypertensive rats. 107 26

1. Prostaglandin E2 significantly inhibits the renin reaction in whole plasma as well as in the isolated system of semi-purified human renin and human renin substrate. The inhibitory effect of prostaglandin A2 was less marked in whole plasma and absent in the isolated system. 2. The inhibitory effect of prostaglandin E2 was more marked in normal than hypertensive plasma and was maximal at the lowest concentration used. In hypertensive plasma the maximal inhibitory effect was achieved at tenfold higher concentrations. 3. In normal plasma prostaglandin E2 does not affect the rate of product formation (k5 = k6), but inhibits the overall renin reaction by decreasing the total amount of available enzyme-substrate and enzyme--substrate modifier complex (K2 less than K3). 4. In hypertensive plasma prostaglandin E2 acts as a potential accelerator of the rate of product formation (k6 greater than k5). In the range of substrate concentration employed, the apparent inhibitory effect is explained by an even greater lack of available complex (K less than K3). This behaviour in hypertensive plasma is consistent with the presence of an additional modifier (? activator).
Clin Sci Mol Med Suppl 1975 Jun
PMID:Effect of prostaglandins (E2 and A2) on the enzymatic reaction of human renin in isolated homologous system and with added normal and hypertensive plasma. 107 83

1. Changes in specific airway conductance after the inhalation of aerosols of prostaglandins (PG) E1, E2, and F2alpha were investigated in healthy and asthmatic subjects. 2. Inhalation of 155 nmol (55 mug) of PGE1 or 156 nmol (55 mug) of PGF2 resulted in consistent minor bronchodilatation in healthy subjects, but in asthmatic patients airway conductance increased significantly, along with subjective improvement. Isoprenaline (988 nmol; 550 mug) inhalation resulted in a similar increase in conductance to that obtained after these two prostaglandins, whereas a control aerosol had no effect. In contrast to the isoprenaline aerosol, both PGE1 and PGF2 were highly irritant to inhale. It was concluded that this made them unsuitable for therapeutic use. 3. Prostaglandin F2alpha inhalation resulted in a dose-related bronchoconstriction in healthy and asthmatic subjects. Asthmatics were approximately 150 than were the healthy subjects but there was very wide and significant variantion in the sensitivity of the asthmatic subjects. In contrast the asthmatic subjects were only 8-5 times more sensitive to histamine than the healthy subjects with less variation in response of individual subjects. The reasons for the hyper-reactivity of asthmatic subjects to PGF2alpha is unknown and no correlation could be drawn between increased sensitivity and age, type of asthma, or treatment. 4. The effects of disodium cromoglycate, flufenamic acid, atropine methonitrate, PGF2 and isoprenaline on PGF2alpha-induced bronchoconstriction were investigated in healthy subjects. Prostaglandin E2 reversed PGF2alpha-induced bronchoconstriction, as did isoprenaline, but prior treatment with the other drugs had no effect in preventing bronchoconstriction.
Clin Sci Mol Med 1975 May
PMID:Effects of inhaled prostaglandins E1, E2, and F2alpha on the airway resistance of healthy and asthmatic man. 112 33

1. Acute renal failure was induced in conscious rate by subcutaneous injection of glycerol. 2. Expansion of the extracellular space by infusion of 150 mmol/l sodium chloride (saline) partly protected the animals against acute renal failure. 3. This protective effect of saline infusion disappeared when the animals were treated with indomethacin. This effect could be reversed by the addition of prostaglandin (PGE2) to the saline infusion. 4. We suggest that prostaglandins may be involved in mediating the protection afforded by saline infusion against acute renal failure due to glycerol.
Clin Sci Mol Med 1975 Nov
PMID:The effect of indomethacin and prostaglandin (PGE2) on renal failure due to glycerol in saline-loaded rats. 119 9

Endothelin (ET) has been shown to contract both vascular and nonvascular smooth muscle and to stimulate human nasal glandular secretion of serous and mucous cell products. Some effects of ET are thought to be mediated by eicosanoid production. To explore the direct effect of ET on arachidonate metabolism in cultured human nasal mucosal explants, eicosanoids were measured after ET-1 stimulation. After labeling the explants with [3H]arachidonic acid (AA), supernatant from control and ET-1-treated explants were fractionated by reverse-phase high-performance liquid chromatography (HPLC). The resulting elution pattern suggested the release of prostaglandin (PG) E2 and AA in response to ET-1 stimulation. Radioimmunoassay after HPLC resolution confirmed that ET-1 induced a significantly increased release of PGE2 as well as PGD2, PGF2 alpha, thromboxane B2, and 15-hydroxyeicosatetraenoic acid (15-HETE). Although significant amounts of 15-HETE were generated, cyclooxygenase product generation was most remarkable. Eicosanoid release after ET-1 exposure (10 to 0.1 microM) is concentration dependent and occurs within 1 h. Whereas 15-HETE release was maximal at 4 h, prostanoid production was maximal 1 h after exposure to ET-1. Other assayed AA metabolites, including the peptidoleukotrienes, did not significantly change after ET-1 stimulation. We conclude that ET-1 induces the release of predominantly cyclooxygenase products from cultured human nasal mucosal explants.
Am J Respir Cell Mol Biol 1992 Feb
PMID:Endothelin-1 stimulates eicosanoid production in cultured human nasal mucosa. 131 93

Although alveolar type II cells in primary culture have been shown to produce eicosanoids and exposure of type II cells to silica in vitro alters eicosanoid production, the production of eicosanoids by alveolar type II cells isolated after acute lung injury in vivo has not been evaluated. Therefore, we investigated the production of arachidonic acid (AA) metabolites by alveolar type II cells isolated after silica-induced lung injury. Alveolar type II cells were isolated from rats 14 days after intratracheal silica instillation and from untreated animals. Type II cells were separated into normotrophic and hypertrophic populations by centrifugal elutriation, and secreted eicosanoids were determined under basal and stimulated conditions by enzyme immunoassay on the day of isolation and after 1 day in culture. Under basal conditions, freshly isolated type II cells from silica-treated animals produced more prostaglandin (PG) E2 than 6-keto-PGF1 alpha or thromboxane B2 (TxB2). Production of all three prostanoids increased with increasing cell size. The calcium ionophore A23187 stimulated a less than 2-fold increase in PGE2 and 6-keto-PGF1 alpha production in all groups of cells. In contrast, this calcium ionophore greatly enhanced TxB2 and leukotriene C4 (LTC4) production by normotrophic type II cells from both untreated and silica-treated animals. Incubation with exogenous AA suggested that the increased capability of the hypertrophic cells to synthesize PGE2 and TxB2 was due primarily to an increase in arachidonate availability. The hypertrophic type II cells also appear to have increased prostacyclin synthase activity. There were no differences in the catabolism of PGE2 between the normotrophic and the hypertrophic type II cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1992 Apr
PMID:Alterations in eicosanoid production by rat alveolar type II cells isolated after silica-induced lung injury. 131 52

Primary cultures of peripheral lung lobes were grown in a highly supplemented medium. Human lung endothelial cells (HLE) were isolated from the mixed population by FACS. The cells proliferated rapidly and were serially cultivated for at least 16 passages. Both early and late passage cells were positive for the standard endothelial markers. Factor VIII related-antigen (Factor VIII R-Ag), angiotensin-converting enzyme, acetylated low-density lipoprotein labeled with 1,1'-dioctadecyl-1,3,3,3',3'-tetramethyl-indocarbocyanine perchlorate (DiI-Ac-LDL) uptake, and bound the lectin Ulex europaeus agglutinin (UEA). Prostaglandin E2 was the major cyclooxygenase product of HLE, in contrast to human umbilical vein endothelial cells (HUVE), which synthesized PGI2 in excess of PGE2. Factor VIII R-Ag exhibited a diffuse cytoplasmic as well as an extracellular fibrillar distribution in HLE, in contrast to a vesicular (Weibel-Palade body) cytoplasmic distribution in HUVE. The HUVE did demonstrate some extracellular fibrillar Factor VIII R-Ag as well. Urokinase was the predominant plasminogen activator (PA) secreted by HLE, whereas tissue PA was predominant in HUVE cultures. HLE formed tube-like structures within 2 h of plating on a Matrigel matrix whereas HUVE formed larger tube-like structures only after 1 or more days. The properties described here indicate that human lung microvessel endothelium can be isolated and continuously grown from small tissue segments and express a number of properties that differ from those of HUVE. These studies provide further support for the concept that endothelial cells from different sources can exhibit considerable heterogeneity relating to their phenotypic and biochemical properties.
Am J Respir Cell Mol Biol 1992 Dec
PMID:Isolation, cultivation, and partial characterization of microvascular endothelium derived from human lung. 133 46

The thyroid epithelium transports fluid bidirectionally using active transport of Na+ ions from apical to basal poles and active transport of Cl- in the reverse direction. In these studies we sought evidence for cyclic AMP activated Cl- channels on the apical membranes of thyroid cells in monolayer culture. A Cl(-)-dependent basal-positive short-circuit current (ISC) was demonstrated in bicameral chambers after blocking Na+ transport with phenamil, and responded to prostaglandin (PG) E2 with a spike of 5-10 min duration followed by a plateau. The onset of the spike coincided with an increase in the conductance of the epithelium. Application of an external Cl- concentration gradient, by replacing the medium in the apical compartment with Cl(-)-free medium, resulted in an increase in ISC after, but not before, addition of PGE2. Forskolin and thyroid-stimulating hormone (TSH), but not A23187, also stimulated Cl- transport. In conjunction with previous observations that Cl- transport was mediated by a bumetanide-sensitive NaKCl2 symporter on the basal membrane, these observations indicated the presence of a cyclic AMP activated Cl- conductance in the apical membrane of thyroid cells.
Mol Cell Endocrinol 1992 Oct
PMID:Chloride conductance of apical membrane in cultured porcine thyroid cells activated by cyclic AMP. 133 5

Five homogenates of human sperm cells were separately incubated with [14C]arachidonic acid in the presence of reduced glutathione, L-tryptophan, and haematin as cofactors. The cyclooxygenase products of arachidonic acid metabolism were extracted, separated, and measured for their radioactivity. The rate of formation of prostaglandin (PG)D2, PGE2, PGF2 alpha, 6-keto PGF1 alpha, and thromboxane (TX)B2 were 18.0 +/- 1.11, 10.9 +/- 0.68, 5.8 +/- 0.21, 3.9 +/- 0.13 and 6.6 +/- 0.52 pmol/10(6) cells/min, respectively. These results are discussed in relation to the hypothesis that cyclooxygenase metabolites of certain polyunsaturated fatty acids play an important part in the sperm acrosome reaction and fertilization.
Mol Reprod Dev 1992 Nov
PMID:Biosynthesis of prostaglandins by human spermatozoa in vitro and their role in acrosome reaction and fertilization. 144 96

Despite the extensive literature on brain eicosanoids, no information is available on the cellular source of individual compounds in the mature organ and the relative contribution of different cell types to the total synthetic product. To address this problem, neurons and glia were isolated from the cerebral cortex of the adult rat by a process comprising, in order, trypsinization, selective sieving, differential centrifugation, and density gradient centrifugation. Enrichment of cells in the appropriate fractions was verified by morphological, immunocytochemical, and biochemical criteria. Both neuron- and glia-rich fractions retained synthetic activity throughout the period of incubation (max. 60 min). Among the eicosanoids examined, prostaglandin (PG) E2 was the predominant compound, followed by leukotriene (LT) E4 and thromboxane (TX) B2, whereas LTC4 occurred in minimal amounts. Although the rank order of eicosanoids did not vary with the cell type, absolute values of PGE2 and TXB2 were greater with neurons. PGE2 synthesis was increased by supplementation of the medium with arachidonic acid (2.6 microM), whereas indomethacin (5.6 microM) had the opposite effect. Conversely, LT synthesis was not altered by arachidonic acid and was only marginally reduced by the 5-lipoxygenase inhibitor, U-60,257 (10 microM). Several agonists (12-O-tetradecanoyl-phorbol-13-acetate, TPA; Ca ionophore A23187; platelet-activating factor; endotoxin; recombinant IL-1) were tested on both neuron- and glia-rich fractions but none of them had an effect. We conclude that freshly isolated neurons and glia are viable insofar as the basal rate of eicosanoid synthesis is concerned. No qualitative difference was noted between the two cell types in the spectrum of products formed and the spectrum itself accorded with early data on the biosynthetic activity of the intact tissue in vivo. Our isolation procedure appears useful for the analysis of the cellular source of eicosanoids under resting conditions, although it cannot be applied to the study of the site and mode of action of activators.
Mol Chem Neuropathol 1992 Dec
PMID:Eicosanoid formation in the rat cerebral cortex. Contribution of neurons and glia. 149 82


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