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1.
Renomedullary tissue from rabbit or rat was incubated with angiotensin I, II, III, arachidonic acid, bradykinin, indomethacin and meclofenamate to study their effect on PGE2 production. Arachidonic acid and bradykinin enhanced PGE2 production significantly. Indomethacin and meclofenamate inhibited PGE2 production by more than 70%. Angiotensin I, II and III did not influence PGE2 production. These results suggest that bradykinin and arachidonic acid stimulate PGE2 production by a direct cellular action whereas the angiotensins do not.  相似文献   

2.
The relationship between aldosterone production and prostaglandin E2 synthesis was evaluated using the responses of isolated rat adrenal glomerulosa cells to angiotensin II, ACTH and potassium. Simultaneous PGE2 and aldosterone measurements were made during timed incubations with these stimuli, and in incubations with arachidonic acid, meclofenamate, indomethacin, and aminoglutethamide. PGE2 and aldosterone production were assessed by radioimmunoassay. We were not able to demonstrate stimulation of PGE2 by angiotensin II, ACTH, or potassium despite significant increments in aldosterone production with these stimuli. Arachidonic acid enhanced PGE2 synthesis, but had no effect on aldosterone release. Indomethacin and meclofenamate inhibited aldosterone secretion. Aminoglutethimide depressed aldosterone production, but had little effect on PGE2 levels in the media.These studies demonstrate that dienoic prostaglandins play no direct role in aldosterone production stimulated by angiotensin II, ACTH, or potassium in rat adrenal glomerulosa cells. Since inhibitors of cyclo-oxygenase decreased aldosterone synthesis, it is possible that fatty acids other than arachidonic acid may be cyclo-oxygenated to products which regulate aldosterone production.  相似文献   

3.
Prostaglandin (PG) synthesis was determined in human embryo lung fibroblasts (HELF) during active, slowed and nongrowing phases. Bradykinin and ascorbic acid were used to induce PG synthesis. The cells were also exposed to arachidonic acid, a PG precursor. During active growth, PGE2 synthesis in response to stimulation by either bradykinin or ascorbic acid was low. As growth slowed the cellular response changed. During quiescence bradykinin and ascorbic acid stimulated PG production markedly while the conversion of free arachidonic acid to PGE2 also increased markedly. This change in response by quiescent cells was not due to an increase in cell density. When growing and quiescent cells at the same cell density were compared, the growing cells showed very little response to bradykinin while the quiescent cells were very responsive. The change in response was also not due to any differences in arachidonic acid concentrations in the culture medium during growth and non-growth.  相似文献   

4.
Minced rat renal medulla was incubated for 30 min at 37 °C in the presence of angiotensin, I, II or III (100 ng/ml) to determine the existence of a direct stimulating effect on prostaglandin (PG) production. PGE2, PGF, 6-keto PGF and Thromboxane B2 (TXB2)_were determined by radioimmunoassay.For analysis of data variance, the results were separated according to whether the net output of PGE2 was above or below 1.5 ng PGE2 equivalent/mg tissue/30 min. Under low-output conditions, angiotensin I, II or III stimulated PGE2 production significantly (p<0.02) and tended to augment PGF production, while under high-output conditions no effect on PGE2 or PGF production was observed.Under either output condition, angiotensin I, II or III had no effect on 6-keto PGF and TXB2.  相似文献   

5.
The activity of prostaglandins (PG) in producing vascular permeability was quantitated by dye extraction method in skin of anaesthetized rabbits. PGE1 and PGE2 (0.01–10 μg) produced increase in vascular permeability. Activity was approximately equal to that of histamine (Hist) and 120 of that of bradykinin (BK) on a weight basis. The activity of PGF and PGF was only 120 of that of PGE1 or PGE2.In spite of the relatively low potency of PGE1 and PGE2 in the rabbit, near threshold doses (0.1 or 1 μg) of PGE2 could potentiate permeability responses to bradykinin (0.1 μg) by 10 or 100-fold, respectively. Equivalent doses (0.1 or 1 μg) of histamine could not potentiate the bradykinin responses. Arachidonic acid (AA) at 1 μg, produced a 10-fold potentiation in the permeability response to bradykinin (0.1 μg). Pretreatment of the rabbits with indomethacin (20 mg/kg, i.p.) reduced the responses of BK (0.1 μg) + AA (1 μg) down to a similar magnitude of those seen with bradykinin alone. However, indomethacin did not block responses to either, BK alone, BK + PGE2, or BK + Hist. Various doses (1, 10, 100 and 300 μg) of arachidonic acid alone also produced increase in cutaneous vascular permeability, although its potency was only 1318 of that of PGE2. This activity of arachidonic acid was attributed in part to its bioconversion to PGE2, since its activity was significantly reduced by the prostaglandin antagonist, diphloretin phosphate (DPP) (60 mg/kg, i.v.) and by indomethacin (20 mg/kg, i.p.), which blocks conversion of arachidonic acid to prostaglandins. Arachidonic acid may owe some of its permeability increaseing effects to histamine release, since its effects were also reduced by the antihistamine, pyrilamine (2.5 mg/kg, i.v.).  相似文献   

6.
《Insect Biochemistry》1987,17(6):863-870
This is the first investigation concerning prostaglandin-like compounds in the primitive insect, Thermobia domestica. The incubation of homogenates of reproductive tissues in the presence of [U-14C]arachidonic acid yielded several compounds which have been characterized by their chromatographic mobilities as well as by the enzyme systems involved in their formation. The three major compounds (I to III) had Rf values very different from those of several prostaglandin standards (PGE2, PGF and 6-keto PGF). As the addition of aspirin or indomethacin had no effect on the conversion of arachidonic acid, a cyclo-oxygenase pathway leading to prostaglandins seems to be excluded. However, another compound (noted V), present in very small quantities, could be a prostaglandin, owing to its chromatographic mobility near that of the PGE2 standard. By contrast, compounds I and II co-migrated with 8- and 5-hydroxyeicosatetraenoic acid standards, respectively, and the addition of 4,7,10,13-eicosatetraynoic acid (ETYA) or nordihydroguaiaretic acid (NDGA) showed a pronounced and dose-dependent inhibition of arachidonic acid conversion. These data demonstrate lipoxygenase activity. Such a pathway in the metabolism of arachidonic acid had not, as yet, been reported in insects. This enzyme system can be demonstrated in the genital tract of the male and also in the seminal receptacle of the female, especially after insemination. So the enzyme system is probably transferred from male to female during mating.  相似文献   

7.
Supplementation of growing MDCK canine kidney tubular epithelial cultures with linoleic acid produced a 3.6- to 4.9-fold increase in bradykinin-stimulated PGE2 release as measured by radioimmunoassay. Under these conditions the cell phospholipids contained 3.9-times more linoleic acid and 5.6-times more arachidonic acid, with the inositol, ethanolamine and choline phosphoglycerie fractions becoming enriched in arachidonic acid. By contrast, supplementation with arachidonic acid did not enhance bradykinin-stimulated PGE2 release even though the arachidonic acid content of the cell phospholipids was increased 8.8-fold. The distribution of radioactive prostaglandin products was unchanged by these fatty acid enrichments, with PGE2 accounting for 55 to 68% of the total output from [1-14C]arachidonic acid. Linoleic acid supplementation also produced a 2.5-fold increase in PGE2 formation stimulated by extracellular arachidonic acid, whereas supplementation during culture with arachidonic acid caused a 55 to 80% inhibition. This difference cannot be accounted for by changes in the ability of the cells to incorporate extracellular arachidonic acid. it is suggested that at least some of the effects of linoleate supplementation on prostaglandin production are due to the resulting enrichment of the intracellular phospholipid substrate pools with arachidonic acid. In addition, it appears that prolonged exposure to arachidonic acid during culture has an overriding inhibitory effect on prostaglandin production even though the total cell lipids bocome highly enriched in arachidonate.  相似文献   

8.
We report here that production and release of PGE2 do not occur in common bacteria. The apparent production in the presence of arachidonic acid, previously reported (1) may be explained by PGE2 contamination and autooxidation of the AA used. The presence of PGE2 like material in some but not all isolates of Propionibacterium acnes is confirmed.  相似文献   

9.
Changes in arterial blood pressure and heart rate were observed in the spontaneous hypertensive (SH) rat following the intravenous administration of arachidonic acid, the precursor of prostaglandin E2 (PGE2). The pronounced fall in blood pressure and the increase in heart rate induced by arachidonic acid were also observed in SH rats receiving either prostaglandin E1 (PGE1) or PGE2. In SH rats receiving various anti-inflammatory agents the cardiovascular responses to arachidonic acid were inhibited, but the blood pressure responses to the E-type prostaglandins were not altered. The data are interpreted to suggest that cardiovascular changes induced by arachidonic acid are mediated via its conversion to PGE2.  相似文献   

10.
In this study, the changes of arachidonic acid metabolites after an ischemia-reperfusion (I/R) period are investigated. The cyclooxygenase and lipoxygenase metabolites were found to be significantly increased after a 45 min period of ischemia followed by 5 min of reperfusion. Prostaglandin E2 (PGE2)- and leukotriene C4 (LTC4)-like activities did not change in the ischemic period, but they both increased after reperfusion. A cyclooxygenase inhibitor indomethacin and lipoxygenase inhibitor nordehydroguaretic acid (NDGA) decreased PGE2- and LTC4-like activities, respectively, while allopurinol and superoxide dismutase (SOD) decreased both activities.According to our results, it can be assumed that free oxygen radicals are responsible for the elevation of PGE2- and LTC4-like activities and both of these arachidonic acid metabolites and free oxygen radicals are the main necrotizing agents in ischemia-reperfusion induced damage.  相似文献   

11.
The process of renal inflammation was examined using the partial renal vein constricted rabbit kidney (RVC) as a model. Forty eight hours of partial renal vein constriction in the rabbit was associated with an increase in prostaglandin (PG) and thromboxane (Tx) production. The perfused RVC kidney showed an enhanced time-dependent increase in PG and Tx production in response to bradykinin stimulation when compared with the unlatered contralateral (CLK) or normal kidney. At 6 hrs of perfusion bradykinin stimulation lateral (CLK) or normal kidney. At 6 hrs of perfusion bradykinin stimulation released 2950±350 ng PGE2, 61±15 ng TxB2 from the RVC, and 225±85 ng PGE2 and undetectable TxB2 from the CLK. Histological examination of the RVC cortex showed an increase in fibroblast-like cells, a modest increase in the interstitial space and an appearance of macrophages and lymphocytes not seen in the normal of CLK. Endotoxin has been reported to stimulate macrophages in culture to produce PGE2 and TxB2. Endotoxin (100 ng)_stimulation of the perfused RVC kidney caused an immediate, followed by a chronically increasing, release of PGs and Tx. Two hours after endotoxin injection 50 ml of effluent fromt the RVC contained 1450±107 ng PGE2 and 15.0±4.5 ng TxB2. Other models of renal inflammation (e.g., the hydronephrotic kidney, chronic glomerulonephritis) also show the histological appearance of macrophages. In addition, hydronephrotic kidneys undergo fibroblast proliferation and changes in arachidonic acid metabolism similar to what we observed in the RVC. This work suggests that the inflammatory process (mononuclear cell infiltration), fibroblast-like cell proliferation, and accompanying changes in arachidonate metabolism) is common among different forms of renal injury.  相似文献   

12.
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). PGF and PGE2 were measured by R.I.A.. A sharp peak PGF 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 PGF 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 PGF. The conversion rate of arachidonic acid into 6 keto PGF is 5 times higher than into PGF. 6 keto PGF was further identified by GC/MS. No significant difference was observed between 6 keto PGF production during oestrus and dioestrus.  相似文献   

13.
The antitumor activity and arachidonic acid metabolism of operationally defined macrophage populations was examined. Macrophages from mice injected with (strain BCG) or with pyran-copolymer were cytotoxic for tumor cells. The major arachidonic acid metabolite of these cells was PGE2. Neither resident nor elicited macrophages were cytotoxic. However, elicited macrophages as well as macrophages from BCG injected mice inhibited tumor cell growth. The production of arachidonic acid metabolites by elicited cells, while low initially, was followed by a rapid increase in PGE2. The major metabolites of resident cells were PGE2 and prostacyclin. The cAMP:cGMP ratio correlated with the metabolic activity of the cells.  相似文献   

14.
The CPAE bovine endothelial cell line may be stimulated to produce eicosanoids. Leukotriene D4 increased the release of arachidonic acid primarily by activating phospholipase A2 while bradykinin activated the phospholipase C pathway. Cells pretreated with dexamethasone, a phospholipase A2 inhibitor, no longer responded to stimulation by LTD4 but did release arachidonic acid when treated with bradykinin. Aspirin blocked bradykinin-stimulated production of arachidonic acid but left the response to LTD4 unaffected. We conclude that these cells produce eicosanoids by activation of both PLA2 and PLC, and that the two different methods of arachidonic acid release can be distinguished by using the common anti-inflammatory drugs aspirin and dexamethasone.  相似文献   

15.
The pattern of prostaglandins produced from arachidonic acid by two sublines of MDCK canine kidney epithelia cells was different. In one subline designated MDCK1, the most prevalent prostaglandin product was PGE2, whereas the most prevalent product in the subline designated MDCK2 was PGF. This difference was observed when cells previously labeled with [1?14C]arachidonic acid were stimulated with either bradykinin or the calcium ionophore A23187, or when prostaglandins were produced from labeled arachidonic acid added directly to the assay medium. In the latter case, the difference was maintained over a 38-fold range of extracellular arachidoante concentrations. These findings indicate the there is a persistent difference in the distribution of prostaglandins produced by the two commonly used sublines of MDCK cells.  相似文献   

16.
In human platelet-rich plasma (PRP) eicosapentaenoic acid (EPA) inhibited platelet aggregation induced by a stable analogue of PGH2 (U46619), arachidonic acid, collagen or ADP. EPA was more potent than oleic, linoleic, α-linolenic or γ-linolenic acids. In aspirin-treated platelets, aggregation induced by U46619 was inhibited to a similar extent by arachidonic acid or by EPA over a range of concentrations of 0.05–0.3 mM. EPA incubated with PRP did not induce the generation of a thromboxane (TXA)-like activity; indeed it prevented the formation of TXA2 induced by arachidonic acid or by collagen. The anti-aggregatory activity of EPA was not influenced by inhibitors of cyclo-oxygenase and lipoxygenase. The anti-aggregatory action of EPA may be caused by a rapid occupancy by EPA of TXA2/PGH2 “receptors” on platelet membrane as well as by a slower displacement of arachidonic acid from platelet phospholipids by chemically unchanged molecules of EPA.Not all samples of PRP were irreversibly aggregated by PGH2, but in those that were, PGH3 also induced an immediate dose-dependent but reversible aggregation. After a 4 min incubation of non-aggregating doses of PGH2 or PGH3 (100–300 nM) with PRP a stable anti-aggregatory compound was detected. The inhibitory activity produced from PGH3 was apparently more potent (ca 10 times) than that obtained from PGH2. The anti-aggregating compounds were identified by TLC and GLC-MS as PGD2 and PGD3. The apparent difference of potency between PGD2 and PGD3 was attributed to the concurrent production of PGE2 and PGE3. PGE2 prevented the inhibitory effect of PGD2 whereas PGE3 did not affect the activity of PGD3.It is concluded that one of the reasons for the low incidence of myocardial infarction in Eskimos could be that the pro-aggregatory arachidonic acid is replaced in their phospholipids by the anti-aggregatory EPA.  相似文献   

17.
We have studied the effects on bone of three structurally dissimilar non-steriodal anti-inflammatory drugs which inhibit prostaglandin cyclo-oxygenase activity (PGH synthase); indomethacin, flurbiprofen, and piroxicam. We used cultures of half calvaria from neonatal or fetal rats to measure effects on PGE2 production, measured by radioimmunoassay. In four day neonatal rat calvaria, indomethacin inhibited PGE2 release into the medium by 80% at 10−8 M, while flurbiprofen and piroxicam produced similar inhibition at 10−6 M. However, at 10−10 M, treatment with all three compounds resulted in an increase in medium PGE2 concentration of 60 to 120%. To assess the mechanism of this effect, bones were labeled with [3H]-arachidonic acid, washed and cultured in the presence or absence of piroxicam. At 10−6 M, piroxicam inhibited production of cyclo-oxygenase products and arachidonic acid release. However, at 10−10 M, there was a substantial increase in labeled products, particularly PGE2, despite a further decrease in arachidonic acid release. In 21 day fetal rat cultures, flurbiprofen was found to increase PGE2 release both in control cultures and cultures which had been incubated with cortisol (10−8 M) to reduce endogenous arachidonic acid release and supplied with exogenous arachidonic acid (10−5 M) to provide a substrate. These results indicate that three potent inhibitors of PGH synthase can, paradoxically, increase prostaglandin production at low concentrations. The effect does not appear to be due to increased arachidonic acid release, and could be due to increased PGH synthase activity.  相似文献   

18.
In newborn pigs, cerebral ischemia abolishes both increased cerebral prostanoid production and cerebral vasodilation in response to hypercapnia and hypotension. Attenuation of prostaglandin endoperoxide synthase activity could account for the failure to increase prostanoid systhesis and loss of responses to these stimuli. To test this possibility, arachidonic acid (3,6, or 30μg/ml) was placed under cranial windows in newborn pigs that been exposed to 20 min of cerebral ischemia. The conversion to prostanoids and pial arteriolar responses to the arachidonic acid were measured. At all three concentration, arachidonic acid caused similar increases in pial arteriolar diameter in sham control piglets and piglets 1 hr postischemia. Topical arachidonic acid caused dosedependent increases of PGE2 in cortical periarachnoid cerebral spinal fluid. 6-keto-PGF and TXB2 only increased at the highest concentration of arachidonic acid (30 μg/ml). Cerebral ischemia did not decrease the conservation of any concentration of arachidonic acid to PGE2, 6-keto-PGF, or TXB2. We conclude that ischemia and subsequent reperfusion do not result in inhibition of prostaglandin endoperoxide synthase in the newborn pig brain. Therefore, the mechanism for the impaired prostanoid production in response to hypercapnia and hypotension following cerebral ischemia appears to involve reduction in release of free arachidonic acid.  相似文献   

19.
Upregulation and activation of phospholipases A2 (PLA2) and cyclooxygenases (COX) leading to prostaglandin E2(PGE2) production have been implicated in a number of neurodegenerative diseases. In this study, we investigated PGE2 production in primary rat astrocytes in response to agents that activate PLA2 including pro-inflammatory cytokines (IL-1β, TNFα and IFNγ), the P2 nucleotide receptor agonist ATP, and oxidants (H2O2 and menadione). Exposure of astrocytes to cytokines resulted in a time-dependent increase in PGE2 production that was marked by increased expression of secretory sPLA2 and COX-2, but not COX-1 and cytosolic cPLA2. Although astrocytes responded to ATP or phorbol ester (PMA) with increased cPLA2 phosphorylation and arachidonic acid release, ATP or PMA only caused a small increase in levels of PGE2. However, when astrocytes were first treated with cytokines, further exposure to ATP or PMA, but not H2O2 or menadione, markedly increased PGE2 production. These results suggest that ATP release during neuronal excitation or injury can enhance the inflammatory effects of cytokines on PGE2 production and may contribute to chronic inflammation seen in Alzheimer's disease.  相似文献   

20.
To elucidate the role of prostaglandins in adrenal steroidogenesis, we studied aldosterone and corticosterone responses to
of prostaglandin E2 (PGE2), prostaglandin F (PGF), prostacyclin (PGI2), and arachidonic acid (AA) in collagenase dispersed rat adrenal capsular and decapsular cells. Whereas adrenocorticotrophic hormone (ACTH) and angiotensin II (AII) stimulated aldosterone production in capsular cells and ACTH stimulated corticosterone production in decapsular cells in a dose dependent fashion, aldosterone and corticosterone production were not stimulated significantly by PGE2, PGF, PGI2, and AA. Although preincubation of dispersed adrenal cells with indomethacin ( ) markedly inhibited PGE2 synthesis, ACTH- and AII-stimulated aldosterone production and ACTH-stimulated corticosterone production were not attenuated despite prostaglandin blockade. These results indicate that prostaglandins are unlikely to play an important role in adrenal steroidogenesis.  相似文献   

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