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1.
KEITH CROWSHAW 《Nature: New biology》1971,231(25):240-242
THIS report describes the biosynthesis of the naturally occurring renal prostaglandins E2 (PGE2) and F2α (PGF2α)1,2 by homogenates and slices of rabbit renal medulla, from endogenous precursors. I have confirmed that rabbit renal cortex contains little prostaglandin and cannot synthesize them from endogenous lipids3. Hamberg has reported that arachidonic acid, which is converted to PGE2 and PGF2α by enzymes present in ram seminal vesicles4, can be efficiently converted to PGE2 and PGF2α by homogenates of rabbit renal medulla3. I have now confirmed that arachidonic acid, added to such medullary homogenates, can increase the quantities of prostaglandins synthesized. There was no evidence that the major prostaglandin biosynthesized, PGE2, was further metabolized to inactive products. 相似文献
2.
Prostaglandin endoperoxides. VII. Novel transformations of arachidonic acid in guinea pig lung 总被引:16,自引:0,他引:16
The following labeled compounds were isolated and identified after incubation of [1-14C]arachidonic acid with guinea pig lung homogenates: 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT), the hemiacetal derivative of 8-(1-hydroxy-3-oxopropyl)-9,12-dihydroxy-5,10-heptadecadienoic acid (PHD), 12-hydroxy-5,8,10,14-eicosatetraenoic acid (HETE), PGE2, PGF2α, 11-hydroxy-5,8,12,14-eicosatetraenoic acid, and 15-hydroxy-5,8,11,13-eicosatetraenoic acid (in order of decreasing yield). Perfused guinea pig lungs released PHD (654–2304 ng), HHT (192–387 ng), HETE (66–111 ng), PGE2 (15–93 ng), and PGF2α (93–171 ng) following injection of 30 μg of arachidonic acid. Thus guinea pig lung homogenates as well as intact guinea pig lung converted added arachidonic acid predominantly into PHD and HHT, metabolites of the prostaglandin endoperoxide PGG2, and to a lesser extent into the classical prostaglandins PGE2 and PGF2α. 相似文献
3.
Alam Farzad Neal S. Penneys Abdul Ghaffar Vincent A. Ziboh Jean Schlossberg 《Prostaglandins & other lipid mediators》1977,14(5):829-837
The biosynthesis of PGE2 and PGF2α was measured in intact peritoneal exudate preparations obtained fom -treated and control C3H mice. Although both the control and stimulated preparations biosynthesized PGF2α and PGE2 from [1–14C] arachidonic acid, the stimulated preparations generated more of both prostaglandins than did nonstimulated preparations, probably as a result of increased synthesis within macrophages. Increased transformation of PGE2 into PGF2α 9-ketoreductase was noted in stimulated preparations when compared to that in control cells. The data suggest that stimulated macrophages are capable of generating increased quantities of PGF2α and therefore might function as one source of this substance in resolving inflammatory reactions. 相似文献
4.
H. Thaler-Dao M. Ramonatxo M. Saintot J. Chaintreuil A.Crastes de Paulet 《Prostaglandins & other lipid mediators》1982,24(2):149-163
prostaglandin biosynthesis by uteri of ovariectomized rats and guinea pigs treated or untreated with oestradiol 17 β, administered subsutaneously, was measured by R.I.A. of PGF2α and PGE2. Incubations with [1-14C] arachidonic acid were also performed and labelled metabolites were analyzed by TLC. The main metabolite in rats was 6 keto PGF1α and in decreasing order of magniture, PGF2α and PGE2. In guinea pig PGF2ga was the main product. Ovariectomy in rats completely changed the pattern of synthesized prostanoids: PGI2 production was doubled when compared to cycling rats and PGE2 increased 10 fold. PGF2α walues were similar to the mean value measured during the cycle. OE2 treatment almost completely inhibited PGI2 synthesis and reduced PGE2 by half. Total PG synthesis in OE2 treated animals was decreased by 5 fold when compared to spayed rats. Endogenous PGFsα synthesis was slightly stimulated. In the guinea pig OE2 treatment of ovariectomized animals increased the total synthesis from 50 per cent. PGF2α was always the main metabolite. In conclusion OE2 regulation of uterine PG synthesis is depending on the animal species and cannot be explained by a unique effect on the cyclooxyhenase, but rather by an interplay on the various enzymes of the arachidonic acid cascade. 相似文献
5.
S.C. Hung N.I. Ghali D.L. Venton G.C. Le Breton 《Prostaglandins & other lipid mediators》1982,24(2):195-206
The effects of prostaglandin F2α on human blood platelet function were investigated. PGF2α at 15 μM completely blocked platelet aggregation induced by 500 μM arachidonic acid or 3 μM U46619 but had no effect on aggregatin induced by 7.5 μM ADP. A similar specificity of action was not obtained with either PGI2 or PGE2. Thus concentrations of PGI2 (3 nM) or PGE2 (20 μ M) which inhibited U46619-induced aggregation by 100% also blocked ADP-stimulated aggregation.The inhibitory properties of PGF2α were not related to increases in platelet cAMP, since direct measurement of intracellular cAMP revealed that 15 μ M PGF2α produced no substantial change in cAMP levels. This finding was in direct contrast to results obtained using either PGI2 or PGE2. Both PGI2 (3 nM) and PGE2 (20 μ M) induced significant increases in platelet cAMP levels.The possibility that PGF2α directly interacts at the platelet TXA2/PGH2 receptor was investigated by measuring [3H]PGF2α binding to isolated platelet membranes. It was found that [3H] PGF2α binding reached equilibrium within 30 min at room temperature and could be 90% displaced by addition of 1000 fold excess of unlabelled PGF2α. Furthermore, when 1000 fold excess of either the TXA2/PGH2 “mimetic” U46619 or the TXA2/PGH2 antagonist 13-azaprostanoic acid was added, specific [3H] PGF2α binding was displaced by 95% and 85% respectively. In contrast, the same molar excess of 6-keto-PGF1α, azo analog 1, or TXB2, caused displacement of only 15%, 20% or 25% of the [3H] PGF2α binding. Scatchard analysis indicated that [3H] PGF2α has two binding sites; i.e., a high affinity binding site with an apparent Kd of 50 nM and a low affinity binding site with apparent Kd of 320 nM. These results suggest that the selective inhibition by PGF2α of AA or U46619-induced aggregation may be mediated through interaction at the platelet TXA2/PGH2 receptor. 相似文献
6.
J.M. Katz T. Wilson S.J.M. Skinner D.H. Gray 《Prostaglandins & other lipid mediators》1981,22(4):537-551
Mouse calvaria were maintained in organ culture for 96 h and endogenous prostaglandin production and active bone resorption (45 Ca release) measured. After a lag phase of 12 h, active resorption increased over the 96 h period. The amounts of prostaglandins released into the culture medium (measured by radioimmunoassay) were highest in the first 24 h of culture. Unless these were removed by preculturing for 24 h, or suppressed by indomethacin, no response to exogenous PGE2, PGF2α or prostaglandin precursors could be demonstrated. Bone resorption was stimulated after preculture by both PGE2 and PGF2α in a dose-dependent manner (10?18M – 10?5M), with PGE2 being the more potent. Collagen synthesis was unaffected by PGF2α, whereas PGE2 (10?5M) had an inhibitory effect. Eicosatrienoic acid did not stimulate bone resorption at lower concentrations (10?7M – 10?5M_, but was inhibitory at 10?4M. Arachidonic acid also inhibited resorption at 10?4M, but at lower concentrations (10?7M – 10?5M0 increased active resorption. This was concomitant with a rise in PGE2 and PGF2α levels, PGE2 production being significantly higher than PGF2α. The effects of PGE2 (10?8M) and PGF2α (10∞M appeared additive: there was no evidence of synergistic or antagonistic effects when varying ratios of PGE2 : PGF2α were employed. 相似文献
7.
J.F. Burka M. Ali J.W.D. McDonald N.A.M. Paterson 《Prostaglandins & other lipid mediators》1981,22(5):683-691
Specific radioimmunoassays were used to demonstrate the synthesis by the guinea pig trachea of 6-keto PGF1α, TxB2, and PGF2α in addition to PGE2. The rank order of both spontaneous and stimulated release was PGE2 > PGF2α > 6-keto PGF1α = TxB2. Ovalbumin-induced prostanoid release from sensitized tissue was antigen-specific. The release was unlikely to be a secondary consequence of tracheal contraction since incubations with calcium ionophore A23187, at a concentration which produces an equivalent magnitude of contraction of sensitized trachea, did not induce a significant PG or Tx production. In contrast, significantly higher prostanoid synthesis was induced by A23187 in unsensitized than sensitized trachea. Thus sensitization altered the profile of arachidonic acid metabolism evoked by the ionophore. 相似文献
8.
Sei-itsu Murota Tokiya Yokoi Ikuo Morita Yo Mori 《Biochemical and biophysical research communications》1978,83(2):679-687
Effect of various prostaglandins on the release of arachidonic acid from [14C]arachidonic acid labeled fibroblasts was studied. Prostaglandin(PG) F2α was found to enhance the release of radioactive arachidonic acid from the cells. The stimulatory effect was dose dependent, and was greater than that of bradykinin. The active compounds can be ranked in potency for the release of arachidonic acid from the pre-labeled cells per cent of control: PGF2α(200.1%)>PGF1α (141.8%)>PGD2 (137.1%)>thromboxane B2 (113.7%)>PGE2 (109.4%). On the other hand, PGI2 showed a strong inhibitory effect on the arachidonic acid release from the pre-labeled cells (the value was only 69% of the control), while 6-ketoPGF1α, an end metabolite of PGI2, had no effect. 相似文献
9.
Aubrey R. Morrison Fergus Thornton Alan Blumberg E.Darracott Vaughan 《Prostaglandins & other lipid mediators》1981,21(3):471-481
Human cortical hydronephrotic microsomes converted [14C] arachidonic acid to [14C] thromboxane B2 as the major metabolic product. Using [14C] PGH2 as substrate, similar enzymatic conversions were noted with HHT>TXB26KPGF1αPGE2PGF2α as the major products. Inhibition of thromboxane synthetase with imidazole 5 mM reduced thromboxane B2 production by 60% and the major product then was 6 keto PGF1α. After addition of imidazole, the metabolic profile showed 6KPGF1αPGE2HHT>PGF2α. Control experiments were carried out using normal cortical tissue obtained from kidneys removed surgically for carcinoma of kidney and rejected for transplantation secondary to fracture as a consequence of blunt trauma. These control kidneys, while they demonstrated an ability to generate thromboxane B2, had much less activity than hydronephrotic kidneys and with PGH2 as substrate PGE2TxB2. In addition, inhibition with imidazole produced mainly PGE2. Thus, like the rabbit and rat, there is enhanced thromboxane and prostacyclin synthesis in human ureteral obstruction and are, therefore, potential vasoactive compounds which may in part be responsible for the hemodynamic alterations occurring in human obstructive uropathy. 相似文献
10.
At low concentrations (i.e., 10?12–10?9 mol/l), PGF1α and PGF2α very intensely stimulated both the DNA-synthetic and mitotic activities of hepatocytes in 4-day-old primary cultures of neonatral rat liver. DNA replication was more intensely enhanced by PGF2α than by PGF1α, whereas mitotic activity was nearly equally affected by the two prostaglandins. On the whole, the growth-promoting activity of PGF1α used by itself or in equimolar mixtures with other prostaglandins (. ., A1, E1, .) mimicked that of arachidonic acid we previously reported (1). On a molar basis, PGF2α by itself stimulated hepatocytes′ DNA synthesis is more powerfully than arachidonate did, and when used in equimolar mixtures with other prostaglandins was at least as potent as arachidonic acid. These observations establish prostaglandins of the F series as quite powerful commitment factors and, though by a lesser degree, also intracycle regulators for neonatal rat hepatocytes in primary culture. However, the understanding of the role(s) of prostaglandins of F and other series in the physiological control of hepatocytes′ proliferative activation must wait the clarification of their interaction(s) with other arachidonate derivative(s) and polypeptide growth factor(s) which also may be involved in the process. 相似文献
11.
Bovine articular chondrocytes, cultured as cell suspensions and monolayers, produced prostaglandin (PG) E2 and PGI2 (assayed as 6 keto PGF1α), rather less PGF2α and irregular quantities of thromboxane (Tx) B2. Addition of foetal calf serum to the medium greatly stimulated PG production (a sixfold increase in PGE2 and a twofold increase in 6 keto PGF1α).Prostanoid production by cell suspension grown in serum-free medium generally plateaued after 24 hours. In the presence of 20% foetal calf serum, prostanoid production in long-term monolayer cultures increased during the first 6 days of culture. Levels of PGE2α levels remained high. Indomethacin (10-6M) inhibited chondrocyte PG production both in the presence and absence of added arachidonic acid (10-4M). Prostanoids produced by chondrocytes may play a role in the modulation of cartilage metabolism . 相似文献
12.
J.A. Simon 《Prostaglandins & other lipid mediators》1978,15(3):383-397
A radioimmunoassay for 6-keto-prostaglandin F1α has been developed. The assay is accurate and sensitive but since the antiserum cross-reacts 5–10% with prostaglandins (PGs) of the E and F series, solvent extraction and thin layer chromatography are required fo absolute specifity. The assay has been validated by comparison with a radiochemical assay and by the use of an inhibitor of 6-keto PGF1α formation, 15-hydroperoxy arachidonic acid. 6-Keto PGF1α was found to have a low cross reaction with antisera directed against PGE2, PGF2α and thromboxane B2. 相似文献
13.
William G. Anderson M.B. Abou-Donia D.B. Menzel 《Prostaglandins & other lipid mediators》1975,10(5):779-788
Prostaglandins released from isolated, ventilated and perfused rat lungs were measured by a simple modification of the Vane technique using the rat stomach fundus as a continuous bioassay tissue. Exogeneously supplied arachidonic acid was converted mainly to PGF2α which was determined by bioassay. A novel method for mixing a stream of inhibitors with the perfusate was used to determine PGF2α in the presence of substrate amounts of arachidonic acid. Using this system the apparent Km for PGF2α production with arachidonic acid as the substrate was found to be 1.90 × 10−4M, while the Ki for aspirin was found to be 2.47 × 10−4M. These kinetic parameters are close to those reported for cell free systems and subcellular fractions suggesting that both substrate and inhibitor have ready access to the site of prostaglandin synthesis. The method appears to be generally useful to determine the effect of drugs and environmental factors on the release of prostaglandins by the lung. 相似文献
14.
Suspensions of dispersed bovine luteal cells prepared by collagenase digestion of luteal tissue specifically bound [3H]Prostaglandin (PG) E1 and [3H]PGF2α. While the number of sites per cell (~ 1.8 × 105) were about the same for both [3H]PGs, the apparent Kds were different: [3H]PGE1 ? 2.4 nM; [3H]PGF2α ? 11 nM. The [3H]PGs binding was inhibited in a dose-dependent manner in the presence of increasing concentrations of unlabeled PGs. Potency order for inhibition of [3H]PGE1 binding was: PGE2 > PGE1 > PGF2α > PGF1α. The corresponding data for [3H]PGF2α was: PGF2α > PGF1α > PGE2 > PGE1. While [3H]PGE1 and [3H]PGF2α bind to their own receptors with high affinity, their affinities for each other's binding were extremely low. Thus, these results demonstrate that luteal cells, like plasma membranes isolated from luteal tissue, contain receptors for PGEs and PGF2α which are discrete with respect to specificity and affinity. 相似文献
15.
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
16.
The conversion of arachidonic acid to prostaglandins (PG's) and thromboxane B2 (TXB2) was investigated in homogenates from fetal and adult bovine and rabbit lungs. Adult bovine lungs were very active in converting arachidonic acid (100 μg/g tissue) to both PGE2 (10.7 μg/g tissue) and TXB2 (6.2 μ/g tissue). Smaller amounts of PGF2α (0.9 μ/g) and 6-oxoPGF1α were formed. Homogenates from fetal calf lungs during the third trimester of pregnancy were quite active in converting arachidonic acid to PGE2, but formed very little TXB2, PGF2α or 6-oxoPGF1α. Homogenates from rabbit lungs converted arachidonic acid (100 μg/g) mainly to PGE2, both before and after birth. The amount of PGE2 formed increased during gestation to a maximum of about 6 μg/g tissue at 28 days of gestation. It then decreased to a minimum (1.5 μg/g) which was observed 8 days after birth, followed by an increase to about 4 μg/g in older rabbits. 相似文献
17.
H. Thaler-Dao M. Saintot M. Ramonatxo C. Chavis A.Crastes de Paulet 《Prostaglandins & other lipid mediators》1982,23(3):347-359
Prostaglandin biosynthesis was studied in the rat uterus during the oestrous cycle. Uterine homogenates were incubated for 20 minutes in the presence of exogenous substrate (2.10−5M). PGF2α and PGE2 were measured by R.I.A.. A sharp peak PGF2α and a smaller peak of PGE2 were observed at prooestrus, 20 h. Another small PGE2 peak occurred at dioestrus II, 15 h. The lowest values of both PGs were found on dioestrus, 15 h. Plasma oestradiol concentration were highest at proestrus, 15 h and 20 h. A sharp progesterone peak occurred at prooestrus, 20 h. The PGF2α peak is next to the oestradiol peak and is superimposable or lags slightly beyond the progesterone peak.Incubation with 14C arachidonic acid and subsequent analysis of extracts by TLC and scanning showed that the major metabolite is PGI2, identified as 6 keto PGF1α. The conversion rate of arachidonic acid into 6 keto PGF1α is 5 times higher than into PGF2α. 6 keto PGF1α was further identified by GC/MS. No significant difference was observed between 6 keto PGF1α production during oestrus and dioestrus. 相似文献
18.
Tetsuji Okuno Kazuoki Kondo Hiromichi Suzuki Takao Saruta 《Prostaglandins & other lipid mediators》1980,19(6):855-864
The effects of prostaglandins E2 (PGE2), I2 (PGI2) and F2α (PGF2α), arachidonic acid and indomethacin on pressor responses to norepinephrine were examined in conscious rats. Intravenously infused PGE2 (0.3, 1.25 μg/kg/min), PGI2 (50, 100 ng/kg/min), PGF2α (1.8, 5.4 μg/kg/min) and arachidonic acid (0.7, 1.4 mg/kg/min) did not change the basal blood pressure. Both PGE2 and PGI2 significantly attenuated pressor responses to norepinephrine, whereas PGF2α significantly potentiated them. Arachidonic acid, a precursor of the prostaglandins (PGs), significantly attenuated pressor responses to norepinephrine. Since the attenuating effect of arachidonic acid was completely abolished by the pretreatment with indomethacin (5 mg/kg), arachidonic acid is thought to exert an effect through its conversion to PGs. On the contrary, intravenously injected indomethacin (0.2–5.0 mg/kg) facilitated pressor responses to norepinephrine in a dose-related manner without any direct effect on the basal blood pressure. These results suggest that endogenous PGs may participate in the regulation of blood pressure by modulating pressor responses to norepinephrine in conscious rats. 相似文献
19.
Sei-itsu Murota Midori Abe Katsuhiro Otsuka Wen-Chang Chang 《Prostaglandins & other lipid mediators》1977,13(4):711-717
Early effects of various prostaglandins on the production of hexosamine-containing substances by cultured fibroblasts, which were derived from a rat carrageenin granuloma, were studied. At the stationary phase, the cells were exposed for 6 h to one of the prostaglandin A1 (PGA1), A2, B1, B2, D2, F1α, F2α, E1, E2 or arachidonic acid in various concentrations ranging from 0.01 to 10 μg/ml for all the stimuli and from 10 pg to 10 μg/ml for PGF2α. The activity of the cells in incorporating 3H-glucosamine into hexosamine-containing substances (acidic) glycosaminoglycans and glycoproteins) during this period was compared with that of control cells. All the stimuli tested showed more or less stimulative effect on the synthesis of hexosamine-containing substances at their specific concentrations. PGF2α was found to be the most potent stimulant and its stimulative effect was found significant even at the low concentration of 100 pg/ml. PGD2, F1α and E2 were the next potent stimuli. Their optimum dose were around 1 μg/ml but they still had significant stimulation at the concentration of 0.01 μg/ml. Effect of PGE2 was rather mild. Stimulation by PGA1, A2, B1 and B2 or arachidonic acid was seen at high dose, and its seemed to be non-specific. The results suggested that these prostaglandins such as PGF2α, D2, F1α and E2 play some important role on regulating the production of intercellular ground substances. 相似文献
20.
T V Zenser C A Herman R R Gorman B B Davis 《Biochemical and biophysical research communications》1977,79(2):357-363
Kidney membrane fractions metabolized [1-14C]PGH2 to TXB2, PGE2, PGF2α, PGD2, 6-keto PGF1α, and HHT. TXA2, as measured by TXB2, was enzymatically formed in cortex microsomes and was identified by thin layer chromatography and gas chromatography - mass spectrometry. PGH2 caused a labile inhibition of cortical PGE2-stimulated adenylate cyclase. PGE2, PGF2α, and PGD2 are stimulators of cortical adenylate cyclase. The inability of two thromboxane synthetase inhibitors, imidazole and 9,11-azoprosta-5,13 dienoic acid, to block PGH2 inhibition suggested that TXA2 was not an obligatory intermediate in this process. Therefore, a potential function of cortical PGH2 is inhibition of adenylate cyclase. 相似文献