共查询到20条相似文献,搜索用时 31 毫秒
1.
O.V. Miller J.W. Aiken R.J. Shebuski R.R. Gorman 《Prostaglandins & other lipid mediators》1980,20(2):391-400
A direct comparison of the relative potencies of the two anti-aggregatory prostaglandins PGI2 and 6-keto-PGE1 showed PGI2 was at least 20 times more potent than 6-keto-PGE1 when tested against ADP-induced human platelet aggregation. This marked difference in potency was even more evident when the ability of PGI2 and 6-keto-PGE1 to stimulate platelet cyclic AMP levels was determined. When cyclic AMP levels were measured direct comparisons were difficult because the respective dose response curves were not parallel, but 10 ng of PGI2 was equivalent to 300 ng of 6-keto-PGE1.PGI2 was also more potent (10–20 times) than 6-keto-PGE1 as a disaggregatory agent, and the disaggregatory activity of both prostaglandins was enhanced by the phosphodiesterase inhibitor 1-methyl-3-isobutylmethylxanthine.PGI2 was also more active than 6-keto-PGE1 as an inhibitor of thrombus formation in dog coronary arteries in vivo. In vivo, 6-keto-PGE1 was at least 10 times less potent than PGI2, the exact difference could not be determined because 6-keto-PGE1 caused significant falls in blood pressure before anti-platelet activity could be detected.PGI2 is an intrinsically more potent anti-aggregatory molecule than 6-keto-PGE1, but these data do not rule out the possibility that some of the activities attributed to PGI2 could be the result of the conversion of PGI2 and/or 6-keto-PGF1α to 6-keto-PGE1. 相似文献
2.
A direct comparison of the relative potencies of the prostaglandins PGI2 and 6-kto-PGE1 to induce renin release was made in the isolated rat kidney, which was perfused with a synthetic medium at constant perfusion pressure.Both prostaglandins stimulated renin release in a dose-dependent manner (0.01 to 1 μM) and with equal potency.Also in the isolated rabbit kidney, PGI2 and 6-keto-PGE1 had the same potency to induce renin release at 1 μM final concentration.Following infusion of 6-keto-PGE1 a small increase of vascular resistance in the rat kidney was observed, whereas in the rabbit kidney no constrictor effect was seen.When perfusate of PGI2 or 6-keto-PGE1-infused rat kidneys were tested for antiaggregatory activity in the ADP induced aggregation of human platelets and compared with authentic standards, the results showed 6-keto-PGE1 passes the kidney essentially unchanged, whereas only 25–40% of the infused PGI2 appear in the venous perfusates, as judged from the recovery of antiaggregatory activity.Analysis of venous perfusates from 3H-PGI2 infused kidneys by high performance liquid chromatography indicates that about 25% of the infused PGI2 remains intact, a major portion of the perfused radioactivity was identified as 6-keto-PGF1α by combined gaschromatography-mass-spectrometry (19).We conclude that the renin-stimulating effect of PGI2 is not secondary to its metabolism to 6-keto-PGE1, as has been suggested in the literature (8). 相似文献
3.
H.L. Lippton B.M. Chapnick A.L. Hyman P.J. Kadowitz 《Prostaglandins & other lipid mediators》1980,19(2):299-310
The effects of 6-keto-PGE1 on vascular resistance and vascular responses to sympathetic nerve stimulation and vasoconstrictor hormones were investigated in the feline mesenteric vascular bed. Infusions of 6-keto-PGE1 into the superior mesenteric artery dilated the mesenteric vascular bed and markedly inhibited vasoconstrictor responses to sympathetic nerve stimulation, norepinephrine and angiotensin II. The effects of 6-keto-PGE1 and PGE1 on vascular resistance and vasoconstrictor responses were quite similar and both substances inhibited responses to nerve stimulation and pressor hormones in a reversible manner. Responses to nerve stimulation, norepinephrine and angiotensin II were inhibited to a similar extent during infusion of 6-keto-PGE1 and PGE1. Results of these studies suggest that 6-keto-PGE1, a newly identified prostaglandin metabolite, and PGE1 possess the ability to inhibit the vasconstrictor effects of sympathetic nerve stimulation and pressor hormones by a nonspecific action on vascular smooth muscle in the feline small intestine. 相似文献
4.
《Prostaglandins and medicine》1979,2(4):277-284
Since prostaglandin E1 (PGE1) is known to have a beneficial effect in hemorrhagic shock, a biologically active derivative of PGE1, 6-keto-PGE1, was examined for its effect on traumatic shock in rats. In sham-operated rats, infusion of 6-keto-PGE1, at a rate of 250 ng/kg/min intravenously decreased arterial blood pressure by 23 mm Hg at 5 hr. In rats subjected to Noble-Collip drum trauma, infusion of 6-keto-PGE1, starting 15 min after the trauma, significantly improved the survival time from 1.0 ± 0.1 hr to 2.6 ± 0.3 hr compared to rats given only the vehicle (i.e., Tris buffer). The improved survival was accompanied by a diminished plasma accumulation of the cardiotoxic peptide, myocardial depressant factor (MDF), and the lysosomal protease cathepsin D. 6-keto-PGE1 also exerted a direct lysosomal stabilizing effect in isolated cat liver lysosomes, as well as reducing cardiac afterload in rats. It is concluded that 6-keto-PGE1 protects in traumatic shock by hemodynamic as well as cytoprotective actions. 相似文献
5.
A method is described for measurement of the cyclooxygenase products, thromboxane,prostacyclin, and prostaglandins (PG), and several prostaglandin metabolites. The procedure involves separation of the compounds by high-pressure liquid chromatography combined with identification and estimation by serologic analysis. These combined procedures have been used to identify and estimate five such products, PGE2, PGE1 PGF2α, PGF1α, and 6-keto-PGF1α, in the culture fluids of dog kidney cells stimulated by a tumor-promoting phorbol diester. The prostaglandin metabolites, 13,14-dihydro-15-keto-PGE2, 13,14-dihydro-15-keto-PF22α, 13,14-dihydro-PGE2, and 13,14-dihydro-PGF2α, were not found in these culture fluids. 相似文献
6.
A.L. Gimeno M. Chaud A. Bonacossa A.M. Franchi M.F. Gimeno 《Prostaglandins & other lipid mediators》1983,26(4):663-676
Dose-response curves for several prostaglandins (PGI2; PGD2; PGF2 and PGE2); BaCl2 or prostaglandin metabolites (15-keto-PGF2α; 13, 14-diOH-15-keto-PGF2α; 6-keto-PGF1α and 6-keto-PGE1 in quiescent (indomethacin-treated) uterine strips from ovariectomized rats, were constructed. All PGs tested as well as BaCl2, triggered at different concentrations, evident phasic contractions. Within the range of concentrations tested the portion of the curves for the metabolites of PGF2α was shifted to the right of that for PGF2α itself; the curve for 6-keto-PGF1α was displaced to the right of the curve for PGI2 and that for 6-keto-PGE1 to the left.It was also demonstrated that the uterine motility elicited by 10−5 M PGF2α and its metabolites was long lasting (more than 3 hours) and so it was the activity evoked by PGI2; 6-keto-PGF1α and BaCl2, but not the contractions following 6-keto-PGE1, which disappeared much earlier. The contractile tension after PGF2α; 15-keto-PGF2α; 13, 14-diOH-15-keto-PGF2α and PGI2, increased as time progressed whilst that evoked by 6-keto-PGF2α or BaCl2 fluctuated during the same period around more constant levels.The surprising sustained and gradually increasing contractile activity after a single dose of an unstable prostaglandin such as PGI2, on the isolated rat uterus rendered quiescent by indomethacin, is discussed in terms of an effect associated to its transformation into more stable metabolites (6-keto-PGF1α, or another not tested) or as a consequence of a factor which might protects prostacyclin from inactivation. 相似文献
7.
《Prostaglandins and medicine》1981,6(5):473-483
The effects of 6-keto-PGE1 on aggregatory responses to arachidonic acid (AA), adenosine diphosphate (ADP) and collagen were studied in human platelet-rich plasma (PRP). In addition, experiments were carried out to determine if these effects correlate with changes in platelet cyclic AMP and cyclic GMP levels. 6-Keto-PGE1 incubated in PRP produced dose-related increases in platelet cyclic AMP levels whereas platelet cyclic GMP levels were unchanged. Control aggregations induced by AA and ADP did not alter cyclic AMP and cyclic GMP levels whereas control aggregations induced by collagen elevated cyclic GMP levels while cyclic AMP levels were unchanged. 6-Keto-PGE1 produced a dose-dependent inhibition of platelet aggregation induced by AA, ADP and collagen and this inhibition correlated with a dose-related increase in cyclic AMP levels. Since 6-keto-PGE1 does not consistently alter cyclic GMP levels in human PRP, the present data support previous studies suggesting that 6-keto-PGE1 produces inhibition of platelet aggregation through the stimulation of cyclic AMP accumulation. 相似文献
8.
Patrick Y-K Wong Kafait U. Malik Dominic M. Desiderio John C. McGiff Frank F. Sun 《Biochemical and biophysical research communications》1980,93(2):486-494
Metabolism of [9-3H]-PGI2 was studied in the isolated Tyrode's perfused rabbit liver. Five products, four radioactive and one non-radioactive, were identified in the perfusate: 19-hydroxy-6-keto-PGF1α, 6-keto-PGF1α, dinor-6-keto-PGF1α, pentanor PGF1α and a 6-keto-PGE1-like substance. The first two, 19-hydroxy-6-keto-PGF1α and 6-keto-PGF1α, represented 5% and 45% respectively, of the total radioactivity; the last two accounted for 39%. The presence of dinor and pentanor derivatives of 6-keto-PGF1α indicated that β -oxidation and oxidative-decarboxylation occurs in the liver as the major metabolic pathway of PGI2. One non-radioactive metabolite which co-migrated with authentic 6-keto-PGE1 was found to inhibit platelet aggregation, having a potency similar to authentic 6-keto-PGE1, and its effect can be eliminated by boiling and by alkali treatment. This metabolite, having similar Rf value on TLC and biological behavior as 6-keto-PGE1, may arise from oxidation of 6-keto-PGF1α via the 9-hydroxyprostaglandin dehydrogenase pathway, as suggested by recovery of tritiated water in the aqueous phase of the perfusate. This material, a potent inhibitor of platelet aggregation, may arise from PGI2 or its hydrolysis product, 6-keto-PGF1α. 相似文献
9.
We studied the effects of two structurally unrelated inhibitors of the fatty acid cyclooxygenase and of alpha and beta adrenergic blockade on the elevated plasma levels of 13,14-dihydro-15-keto-prostaglandin (PG)E2, 6-keto-PGF1α and thromboxane(TX)B2, the stable derivatives of PGE2, PGI2 (prostacyclin) and TXA2, respectively, in rats with streptozotocin-induced diabetic ketoacidosis (DKA). Meclofenamic acid and indomethacin each produced a significant decrease in the elevated plasma levels of 13,14-dihydro-15-keto-PGE2, 6-keto-PGF1α and TXB2. Phentolamine significantly reduced the plasma level of TXB2 but had no effect on the elevated circulating levels of glucose, free fatty acids, total ketones, 13,14,-dihydro-15-keto-PGE2 or 6-keto-PGF1α. Propranolol significantly reduced the elevated circulating levels of glucose, free fatty acids and total ketones but had no effect on the levels of the three prostaglandin derivatives. The ability of meclofenamic acid and indomethacin to reduce the plasma levels of 13,14-dihydro-15-keto-PGE2, 6-keto-PGF1α and TXB2 confirms that the plasma levels of these three derivatives are elevated in rats with DKA. Since abnormalities in the production of PGI2 and perhaps other cyclooxygenase derivatives may contribute to the pathogenesis of certain important hemodynamic and gastrointestinal features of DKA, cyclooxygenase inhibitors may play a role in the management of selected patients with this disorder. Alpha adrenergic activity is essential for the maintenance of the elevated plasma TXB2 level in rats with DKA. The fall in the plasma TXB2 level during alpha adrenergic blockade appears to reflect inhibition of platelet aggregation and platelet TXA2 production, but other sources of the elevated plasma TXB2 level in DKA are not excluded. Beta adrenergic activity contributes to the maintenance of elevated circulating levels of glucose, free fatty acids and total ketones in experimental DKA but not to the elevated plasma levels of the prostaglandin derivatives. 相似文献
10.
Fluorescent/ultraviolet absorbing ester derivative formation and analysis of eicosanoids by high-pressure liquid chromatography 总被引:1,自引:0,他引:1
A method is described for the quantitative analysis of eicosanoids (arachidonic acid metabolites, nee, prostaglandins) by reverse-phase high-pressure liquid chromatography following formation of the ester derivative with p-(9-anthroyloxy)phenacyl bromide. The lower limit of detection of the eicosanoid ester is 280 pg (ultraviolet—254 nm) and approximately 50 pg (fluorescence 249 emission, 413-nm cutoff). We separated the esters of seven common eicosanoids by reverse-phase chromatography with acetonitrile and water. Thromboxane B2 chromatographs as two species and coelutes with PGF2α. Separation of all others is adequate, including the three metabolites of prostacyclin (6-keto-PGF1α, 6-keto-PGE1, 13,14-dihydro-6,15-diketo-PGF1α). We obtained good correlation between radioimmunoassay and derivative analysis of standard 6-keto-PGF1α extracted from lactated Ringer's solution with standard technique, as well as 6-keto-PGF1α quantitation from tissue culture medium that had contained pulmonary endothelial cells. This method should be applicable to analysis of eicosanoids extracted from biological matrices. 相似文献
11.
《Prostaglandins and medicine》1980,4(4):227-237
Cyclooxygenase products of arachidonic acid metabolism in the plasma of normal rabbits and animals bearing the VX2 carcinoma were separated by high performance liquid chromatography and the effluent fractions assayed by serologic methods. The products measured were 6-keto-PGFlα, thromboxane B2, PGE2, PGF2α, 13,14-dihydro-PGE2, 13,14-dihydro-15-keto-PGE2, 15-keto-PGE2, and 13,4-dihydro-15-keto-PGF2α. In hypercalcemic, tumor-bearing rabbts, the plasma concentrations o 13,14-dihydro-15-keto-PGE2 and 13,14-dihydro-15-keto-PGF2α were markedly elevated (in the range of 0.5 to 16 ng/ml). Previously unmeasured 6-keto-PGF1α, thromboxape B2, 13,14-dihydro-PGE2 and 15-keto-PGE2 were not found in high concentrations in the plasma of tumor-bearing rabbits. These results add further support to our conclusion that the VX2 tumor produces hypercalcemia in the host by a mechanism which utilizes PGE2, rather than a subsequent metabolite of this prostaglandin, as the mediator between the neoplasm and bone. 相似文献
12.
Accumulation of Cyclooxygenase Products of Arachidonic Acid Metabolism in Gerbil Brain During Reperfusion After Bilateral Common Carotid Artery Occlusion 总被引:22,自引:7,他引:15
: Several of the cyclooxygenase products of arachidonic acid were measured in the cerebral hemispheres of gerbils subjected to transient interruption of the cerebral circulation. The levels of PGD2, PGF2α, PGE2, TXB2, 13,14-H2-15-keto-PGE2, and the stable nonenzymic product of prostacyclin, 6-keto-PGF1α, were not altered at the end of a 5-min period of ischemia. However, the onset of reperfusion was accompanied by a rapid accumulation of these products. Levels were highest during the initial period of reperfusion, then decreased to approach control levels after 120 min. PGD2, PGF2α, and PGE2 were the predominant metabolites detected. This postischemic accumulation of arachidonic acid metabolites could be blocked by prior administration of inhibitors of cyclooxygenase activity. 相似文献
13.
《Prostaglandins, Leukotrienes and Medicine》1982,8(4):311-316
We have investigated the possibility that pulmonary biosynthesis of prostacyclin and thramboxane A2 (TXA2) may be affected by variations in PO2. Fresh lung ha ogenates from 8 dogs were incubated for 1 hour at 37°C in Krebs-Ringer solution, at high (492 mnHg) or low (53 mmHg) PO2. After incubation, the stable metabolites of prostacyclin (6-keto-PGF1) and of TXA2(TXB2) were measured by radioimunoassay. The basal (“pre-incubtion”) levels of these metabolites, measured in tubes in which biosynthesis was arrested by the addition of indomethacin (10 g/ml), were 0.76 ± 0.15 and 0.76 ± 0.11 ng/mg wet wt. for 6-keto-PGF1α, in high and low PO2 respectively, and 0.97 ± 0.09 and 0.82 ± 0.15 × 10−1 ng/mg wet wt. for TXB2, in high and low P02 respectively. Synthesis during incubation in other tubes was estimated by subtracting basal values from those measured at the end of incubation. More 6-keto-PGF1α was formed in homogenates exposed to low PO2 (3.01 ± 0.45) than in those exposed kept at high PO2 (1.89 ± 0.37, p< 0.001), but equal amounts of TXB2 were found under both conditions. These results suggest that hypoxia may stimulate pulmonary prostacyclin synthesis; a pulmonary vasodilator, prostacyclin may help modulate hypoxic vasocontriction in the lung. 相似文献
14.
Yu-Hsiang Yu Yi-Cheng Chang Tseng-Hsiung Su Jiun-Yi Nong Chao-Chin Li Lee-Ming Chuang 《Journal of lipid research》2013,54(9):2391-2399
Adipocyte differentiation is a multistep program under regulation by several factors. Peroxisome proliferator-activated receptor γ (PPARγ) serves as a master regulator of adipogenesis. However, the endogenous ligand for PPARγ remained elusive until 15-keto-PGE2 was identified recently as an endogenous PPARγ ligand. In this study, we demonstrate that zinc-containing alcohol dehydrogenase 2 (ZADH2; here termed prostaglandin reductase-3, PTGR-3) is a new member of prostaglandin reductase family that converts 15-keto-PGE2 to 13,14-dihydro-15-keto-PGE2. Adipogenesis is accelerated when endogenous PTGR-3 is silenced in 3T3-L1 preadipocytes, whereas forced expression of PTGR-3 significantly decreases adipogenesis. PTGR-3 expression decreased during adipocyte differentiation, accompanied by an increased level of 15-keto-PGE2. 15-keto-PGE2 exerts a potent proadipogenic effect by enhancing PPARγ activity, whereas overexpression of PTGR-3 in 3T3-L1 preadipocytes markedly suppressed the proadipogenic effect of 15-keto-PGE2 by repressing PPARγ activity. Taken together, these findings demonstrate for the first time that PTGR-3 is a novel 15-oxoprostaglandin-Δ13-reductase and plays a critical role in modulation of normal adipocyte differentiation via regulation of PPARγ activity. Thus, modulation of PTGR-3 might provide a novel avenue for treating obesity and related metabolic disorders. 相似文献
15.
Experiments in vitro demonstrate, that there are different patterns of PG-biosynthesis in the corpus luteum and in the follicles containing cortical substance of the human ovary. In the follicles 6-keto-F1α. the transformation product of prostacyclin, is the main fraction; prostaglandins F2α and E 2 being of inferior importance with regard to their amounts. The formation of the corpus luteum is in close correlation with a strongly increased prostaglandin E2 and a diminished prostacyclin biosynthesis; prostaglandin F2α hardly seems to be involved in this process.By means of indomethacin the formation of all three examined prostaglandins can be prevented almost completely, in the cortical substance as well as in the corpus luteum. LH (or HCG) at concentrations ranging from 2 ng to 20 μg per ml homogenate produce no stimulating effect of statistical significance on the rate of biosynthesis in both tissues. 相似文献
16.
F. Coceani E. Bodach E.P. White P.M. Olley 《Prostaglandins & other lipid mediators》1980,19(1):109-113
6-Keto-PGE1 is nearly as potent as PGE2 in relaxing the ductus arteriosus of fetal lambs. This finding raises the possibility that 6-keto-PGE1, if occuring naturally as a by-product of PGI2 transformations, may contribute to prenatal patency of the vessel. 相似文献
17.
J.E. Lock P.M. Olley F. Coceani F. Hamilton G. Doubilet 《Prostaglandins & other lipid mediators》1979,18(2):303-309
6-Keto-PGE1 is a potent direct dilator of the pulmonary and systemic circulations of the newborn lamb under both normoxic and hypoxic conditions. Its threshold dose is similar to that of PGI2 and PGE1. Under hypoxia, 6-keto-PGE1 appears equally effective on the pulmonary and systemic circulations, while under normoxia it predominantly affects the systemic circulation. 相似文献
18.
The use of mercaptoethanol in the assay of rat kidney 15-hydroxyprostaglandin dehydrogenase (PGDH) was found to have minimal effect on activity assayed with the spectrophotometric and substrate loss assays. However, mercaptoethanol appeared to inhibit PGDH when assayed by thin-layer chromatography, based upon conversion of 3H-PGE1 to 15-keto-3H-PGE1. Mercaptoethanol reacted with 15-keto-PGE1 to alter its chromatographic mobility and to suppress the U.V. absorption spectrum of 15-keto-PGE1. The implication of the use of ME in radiometric assays is discussed. 相似文献
19.
Christopher W. Benjamin Nancy K. Hopkins Thomas D. Oglesby Robert R. Gorman 《Biochemical and biophysical research communications》1983,117(3):780-787
Leukotriene C4 (LTC4) and, to a lesser extent, leukotriene D4 (LTD4) concentration dependently stimulate prostacyclin (PGI2) biosynthesis in cultured human umbilical vein endothelial cells. PGI2 biosynthesis was quantitated by radioimmunoassay and its structure confirmed by gas chromatography/mass spectrometry. Preincubation of endothelial cells with LTC4 resulted in desensitization to subsequent LTC4 stimulation. However, PGI2 biosynthesis in response to thrombin, PGH2 and arachidonic acid was not inhibited by preincubation with LTC4. The C-6-sulfidopeptide leukotriene receptor level antagonist FPL-55712 attenuates LTC4, but not thrombin-stimulated PGI2 biosynthesis. These data suggest that human umbilical vein endothelial cells have a C-6-sulfidopeptide leukotriene receptor, and that stimulation of this receptor results in PGI2 biosynthesis. 相似文献
20.
Ken-ichi Kiyomiya Kohji Yamaki Noriyuki Nimura Toshio Kinoshita Sachiko Oh-ishi 《Prostaglandins & other lipid mediators》1986,31(1):71-82
White cells were collected from the wash of rat pleural cavity after exsanguination. The incubation mixture of the pleural cells with 1 μM phorbol myristate acetate (PMA) was extracted with acidified ethanol and purified with a Sep-pak C18. The resultant fraction containing prostaglandins (PG) and thromboxane (TX) was allowed to react with 9-anthryldiazomethane (ADAM). After removing contaminants and degraded reagent by silica gel Sep-pak, samples were applied to reversed phase high performance liquid chromatography of octadecylsilyl silica gel and monitored by a fluorescent detector. ADAM derivatives of the authentic PGD2, PGE2, PGF2α, 6-keto-PGF1α, 6-keto-PGE1, TXB2, 15-keo-PGE2, 13, 14-dihydro-15-keto-PGF2α and 13, 14-dihydro-15-keto-PGE2 showed linear regression lines of peak heights within a range of 0.5–25 ng.By using this method PGD2, 6-keto-PGF1α and TXB2 were detected in the incubation mixture of the rat pleural cells with PMA. The result clarified the origin of these PGs and TX found in the exudate of rat pleurisy induced by PMA.ADAM method for HPLC with a help of clean-up by Sep-pak could be a useful tool for detection of a series of arachidonate metabolites in biological materials. 相似文献