首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到20条相似文献,搜索用时 31 毫秒
1.
Administration of PGF (0.2–6.4 μg) into the lateral cerebral ventricle (i.c.v.) induced dosedependent increases in blood pressure, heart rate and body temperature in urethane-anaesthetised rats, but had no effect on these parameters when the same dose range was administered intravenously. Peripheral pretreatment with sodium meclofenamate (50 mg/kg s.c.) shifted all the dose-response curves for PGF (i.c.v.) to the left, but indomethacin (50 mg/kg s.c.) did not significantly affect those changes. Central pretreatment with sodium meclofenamate or indomethacin (1.25 mg per rat i.c.v.) failed to modify significantly the effects of centrally administered PGF.The results support previous suggestions that PGF may participate in the central control of the cardiovascular and thermoregulatory systems, and also suggest that there may be differences in the sites and/or modes of action between sodium meclofenamate and indomethacin.  相似文献   

2.
Prostacyclin (PGI2) induced a dose-dependent decrease in blood pressure with slight increases in heart rate and body temperature, when administered at the doses of 0.1–100 μg into the lateral cerebral ventricle (i.c.v.) of the urethane-anaesthetised rat. When the same doses were administered intravenously, both the blood pressure and heart rate decreased. Central pretreatment with sodium meclofenamate (1 mg/rat i.c.v.) antagonised the central hypotensive effect of PGI2 but i.c.v. pretreatment of the rats with indomethacin (1 mg/rat) failed to affect the PGO2-induced hypotension. Central pretreatment with two histamine H2-receptor antagonists, cimetidine (500 μg/rat i.c.v.) or metiamide (488 μg/rat i.c.v.), antagonised the blood pressure lowering effect of 0.1 μg dose of PGI2 but failed to affect the hypotension induced by higher PGI2 doses. Therefore the main central hypotensive effect of PGI2 seems not to be associated with the stimulation of histamine H2 -receptors in the brain.The hypotensive effect of i.c.v. administered PGI2 appears to be due to an action upon the central nervous system rather than to a leakage into the peripheral circulation. This assumption is supported by the fact that sodium meclofenamate i.c.v. antagonished the effect of PGI2. In addition, the chronotropic response to i.c.v. PGI2 was opposite to that induced by intravenous administration. The results also suggest that there may be differences in the mode of action between sodium meclofenamate and indomethacin.  相似文献   

3.
We cultured phagocytic cells derived from the thymic reticulum in order to study the regulation of prostaglandin (PG) production by antiinflammatory or immunostimulating agents. The kinetics of PGE2, 6-keto-PGF and PGF production were measured by specific radioimmunoassays of the supernatants harvested from cells treated with dexamethasone, a steroidal antiinflammatory drug and by two non steroidal inhibitors (indomethacin and sulindac) or by various immunostimulating agents, one of them, RU 41740 is currently being used in humans. Our results revealed that ech of these drugs exerts a differential effect on the PG production, with a striking action on PGE2 synthesis, a lesser effect on 6-keto-PGF production and almost no effect on PGF synthesis. The possible mechanisms responsible for this complex regulation of PG production are discussed.  相似文献   

4.
The interaction of vasopressin (VP) and prostaglandins (PG) on the nonpregnant human uterus was studied and . In organ baths arginine (A)- and lysine (L)-VP in concentrations of 0.6 to 100 ng/ml stimulated small human myometrial strips and uterine artery preparations to a similar degree. When these VPs were given in the presence of indomethacin or naproxen in concentrations of 1 μg/ml and 5 μg/ml, respectively, the myometrial and arterial responses were not significantly influenced. PGF in concentrations of 0.01–100 ng/ml stimulated the myometrial preparations but caused a slight relaxation of the arteries, with PGE2 the myometrial effects were insignificant and the relaxation of the arteries greater. When AVP was given together with either of the PGs to the bath the result was generally a summation of the individual effects of both types of substances. - In vivo during intrauterine pressure recordings in nonpregnant women 1–2 days before onset of menstruation LVP in single intravenous injection of 1.2 μg markedly stimulated uterine contractions. The response remained practically unaltered after pretreatment with 500 μg of naproxen given orally. The responses to LVP were also closely similar before, during and after intravenous infusion of PGF at a rate of 5 μg/min. - It is concluded that the effect of VP on myometrium and uterine arteries is not to any great extent mediated by local synthesis of PG and that PGs do not cause potentiation or inhibition of the VP effects on the nonpregnant uterus.  相似文献   

5.
The effects of prostaglandin (PG)F and PGF, 1–15 lactone were compared in luteal phase, non-pregnant and in early pregnant rhesus monkeys. Animals treated with either PG after pretreatment with human chorionic gonadotropin (hCG) had peripheral plasma progesterone concentrations that were not statistically different from those in animals treated with hCG and vehicle. However, menstrual cycle lengths in monkeys treated with PGF, 1–15 lactone were significantly (P <0.02) shorter than those in vehicle treated animals. In the absence of hCG pretreatment, plasma progesterone concentrations were significantly (P <0.008) lower by the second day after the initial treatment with either PGF or PGF, 1–15 lactone than in vehicle treated monkeys. Menstrual cycle lengths in monkeys treated with either PG were significantly (P <0.04) shorter than those in animals treated with vehicle. There were no changes in plasma progesterone concentrations in early pregnant monkeys treated with PGF, and pregnancy was not interrupted. In contrast, plasma progesterone declined and pregnancy was terminated in 5 of 6 early pregnant monkeys treated with PGF, 1–15 lactone. These data indicate that PGF, 1–15 lactone decreases menstrual cycle lengths in non-pregnant rhesus monkeys. More importantly, PGF, 1–15 lactone terminates early pregnancy in the monkey at a dose which is less than an ineffective dose of PGF.  相似文献   

6.
The influence of prostaglandins (PG) F2α and E2 on milk ejection, mammary artery blood flow and arterial blood pressure was studied in lactating cows. Injections of both PG in the jugular vein or the carotid artery induced milk ejection after a relatively long latency period. The minimal effective dose amounted to 1 to 5 μg and to 100 to 300 μg for PGF2α and PGE2 respectively. In several cases with PGF2α and once with PGE2 milk ejection was accompanied with a simultaneous increase in blood flow through the mammary artery whereas arterial blood pressure remained unchanged. Both routes of administration showed the same response. It was suggested that the effect of the PG on the bovine myoepithelium is indirect, possibly secondary to a release of oxytocin from the neurohypophysis.  相似文献   

7.
Hydrocortisone (10 μg/ml) had no effect on the basal outputs and A23187-stimulated outputs of PGF, PGE2 and 6-keto-PGF from the Day 15 guinea-pig uterus superfused . These findings indicate that the high output of PGF from the guinea-pig uterus during the last one-third of the oestrous cycle is not modulated by the adrenal glucocorticoid hormones. Progesterone (10 gmg/ml) had no effect on the A23187-induced increases in PG output from the Day 15 guinea-pig uterus. However, oestradiol (10 gmg/ml but not 1 μg/ml) significantly reduced the increases in outputs of PGF, PGE2 and 6-keto-PGF induced by A23187 from the Day 15 guinea-pig uterus, without affecting basal PG outputs. The increase in uterine tone induced by A23187 in the Day 15 guinea-pig uterus was reduced by 20–50% by oestradiol (10 μg/ml). The addition of oestradiol (10 μg/ml) and progesterone together (10 gmg/ml) produced the same effects on the Day 15 guinea-pig uterus as oestradiol alone. Oestradiol (10 μg/ml) also reduced the A23187-induced increases in PG output from the Day 7 guinea-pig uterus, but did not reduce the increase in uterine tone. Oestradiol (10 gmg/ml) reduced the increases in outputs of PGF, PGE2 and 6-keto-PGF induced by exogenous arachidonic acid from the Day 7 and Day 15 guinea-pig uterus. Previous studies have shown that oestradiol is not a cyclo-oxygenase inhibitor. The present findings suggest that oestradiol, at a relatively high concentration, may interfere with the access of arachidonic acid to the cyclo-oxygenase enzyme. This action of oestradiol may explain its anti-luteolytic action when administered to guinea-pigs in large doses after Day 9 of the cycle.  相似文献   

8.
The effects of oestradiol, oxytocin, progesterone and hydrocortisone on prostaglandin (PG) output from guinea-pig endomerium, removed on days 7 and 15 of the oestrous cycle and maintained in tissue culture for 3 days, have been investigated. Oetradiol (3.7 to 3700nM) and oxytocin ( 2 to 200pM) did not stimulate endometrial PGF output, thus not confirming the findings of a previous report (Leaver & Seawright, 1928), nor did they stimulate the outputs of PGE2 and 6-keto-PGF. In fact, oestradiol (3700nM) inhibited the outputs of PGF, PGE2 and, to a lesser extent, 6-keto-PGF. Progesterone (3.2 to 3200nM) inhibited the outputsof PGF and PGE2; hydrocortisone (2.8 to 2800nM) had no effect on endometrial PG output. These findings indicate that the inhibitory effect of progesterone on endometrial PG synthesis and release in the guinea-pig is not due to progesterone having a glucocorticoid-like action. Furthermore, progesterone had no effect on 6-keto-PGF output, suggesting that the mechanisms controlling endometrial PGI2 synthesis (as reflected by measuring 6-keto-PGF) are different from those controlling endometrial PGF and PGE2 synthesis.  相似文献   

9.
Pregnancies in hamsters may be terminated with 10 μg PGF administered b.i.d. on days 4, 5 and 6 of gestation. Small (250 μg and above) daily injections of progesterone on the same days will reverse this PG effect; in contradistinction, 10 mg of progesterone per day failed to maintain normal pregnancies in hamsters spayed on day 5. Daily administration of 3 mg of progesterone and 1 μg of estrone essentially normalized the gestation; administration of PGF at 10 mg on days 5, 6 and 7 of pregnancy in steroid-maintained rats, resulted in pregnancy termination in all animals, while 1 mg was partly effective. These data demonstrate an extra-ovarian site of action of prostaglandin F on pregnancy in hamsters.  相似文献   

10.
Pretreatment of human lung fibroblasts with PGE2 but not PGF enhanced synthesis of prostaglandins (PGs). The effect of the pretreatment on PG synthesis was related to the concentration of PGE2 that was added to the culture medium. Pretreatment with PGE2 at 5 × 10−12M did not enhance PG synthesis whereas pretreatment with PGE2 at 5 × 10−6M induced a maximal effect. Production of PGs was increased following 1 day of pretreatment with PGE2 and was increased further following 3 days of pretreatment. The PGE2 treated cells showed only a slight increase in the bradykinin-induced release of radioactivity from cells prelabeled with [3H]arachidonic acid but showed a dramatic increase in the bradykinin-induced synthesis of radio-labeled PGs. The conversion of free arachidonate to PGs in both intact cells and in a cell-free preparation was increased by PGE2 pretreatment. The presence of cyclohexamide during the pretreatment did not inhibit the PGE2-induced activation of PG synthesis. Taken together, the results indicate that pretreatment of cells with PGE2 increased PG synthesis by augmenting the conversion of arachidonate to PGs.  相似文献   

11.
The present study was to determine whether clonidine could induce calcitonin gene-related peptide (CGRP) production and the underlying mechanisms. Human umbilical vein endothelial cells were treated with clonidine and the dose–effect or time–effect relationship of clonidine on CGRP production was examined. Youhimbine (a α2-adrenoceptor blocker) and l-NAME (an antagonist of nitric oxide synthase, NOS) were chosen to explore the role of α2-adrenoceptor and nitric oxide pathway in the effect of clonidine on endothelial cell-derived CGRP production. The level of CGRP mRNA or protein was detected by Real Time-PCR or radioimmunoassay. Nitric oxide content was measured by nitroreduction assay. The study showed that clonidine was able to induce CGRP mRNA (α- and β-isoforms) expression in a dose-dependent manner in endothelial cells. The effect of clonidine on endothelial cell-derived CGRP synthesis and secretion was attenuated in the presence of youhimbine. l-NAME treatment could also inhibit clonidine-induced CGRP synthesis and secretion concomitantly with the decreased NO content in culture medium. These results suggest that clonidine could stimulate CGRP synthesis and secretion in endothelial cells through the activation of α2-adrenoceptor, which is related to the NO pathway.  相似文献   

12.
Prostaglandin (PG) E2 was the major PG released from the superfused guinea-pig uterus on Day 7, followed by in descending order 6-oxo-PGF, thromboxane (TX) B2 and PGF. However, the outputs of all four substances were low and were very similar. By Day 15, PGF output from the superfused uterus had increased 21.9-fold, whereas the outputs of PGE2, 6-oxo-PGF and TXB2 had increased only 1.8-, 2.9- and 1.2-fold, respectively. A mechanism is apparently “switched on” between Days 7 and 15 which causes a fairly specific increase in the release of PGF from the uterus.Progesterone and/or estradiol had no effect on PG or TX release when superfused over the uterus on Day 7, nor did they have any effect on PG and TX release from the Day 15 uterus when administered separately. When administered together, however, they significantly inhibited PGF, PGE2 and 6-oxo-PGF, but not TXB2, release from the Day 15 uterus. Oxytocin had no effect on PG release from the Day 7 or Day 15 uterus, while A23187 stimulated PGF, 6-oxo-PGF and, to a lesser extent, PGE2 release from the uterus on both Days 7 and 15 Oxytocin is apparently not important for stimulating PGF release from the guinea-pig uterus in relation to luteolysis, whereas increasing intracellular free Ca++ levels may be part of the mechanism for “switching on” uterine PG synthesis. Furthermore, changes in intracellular free Ca++ levels in the endometrium may be responsible for the pulsatile nature of PGF release from the uterus.  相似文献   

13.
Modulation of prostaglandin (PG) biosynthesis by cytosolic fractions derived from homogenates of human amnion, chorion laeve, decidua vera and placenta was examined. PGF and 6-oxo-PGF synthesis by bovine seminal vesicle (BSV) PG synthase was stimulated by the cytosolic fractions of each tissue in a dose-dependent manner. The cytosols from decidua vera and placenta were the most effective in stimulating synthesis and also stimulated PGE2 biosynthesis. Reduced glutathione (GSH) acted to increase the biosynthesis of PGE2 at the expense of other PGs both in the presence and absence of various cytosols. These data are indicative that the mode of action of cytosolic fractions on the stimulation of PG biosynthesis is unlike that of GSH. Indomethacin and aspirin, inhibitors of fatty acid cyclooxygenase activity, strongly inhibited the cytosol-induced stimulation of BSV PG synthase.The cytosolic factors that stimulated PG biosynthesis exhibited differential behavior towards boiling and dialysis. The stimulatory effect of all cytosolic fractions was sensitive to boiling except in the case of chorion leave effects toward 6-oxo-PGF production. In dialysis studies we found that the cytosolic components that stimulated the production of PGF were not removed by dialysis except in the case of cytosol of placenta whereas the stimulatory effects of various cytosols toward the biosynthesis of PGE2 and 6-oxo-PGF were removed by dialysis. These results are indicative of the presence of endogenous factors in human intrauterine tissues that preferentially stimulate the biosynthesis of PGF and 6-oxo-PGF and are further suggestive that PC biosynthesis in intrauterine tissues is, at least in part, regulated by cytosolic factors.  相似文献   

14.
Explants from term human placentas were maintained in culture with daily changes of medium. Daily output of PGF and PGFM1 decreased during the course of the incubation. Addition of 4 μg/ml DHEAS or 67 μg/ml LDL cholesterol had no effect on output of PGF or PGFM. Addition of 1.6, 3.2, or 6.4 μg/ml of LHRH to the culture plates had no effect on output of PGFM or PGF, but LHRH increased hCG output. Dibutyryl cAMP (1mM, 2mM, and 4mM) increased output of PGF, PGFM, and hCG. Aromatase inhibitor decreased hCG output, but it was without effect on output of PGF, or PGFM. Significant correlations were demonstrated between progesterone, PGFM, PGF, and hCG, suggesting that PGF originates in the syncytiotrophoblast cell. The ability of LHRH to stimulate output of hCG but not PGF while dbcAMP stimulated both suggests that either PGF and hCG arise in different cells or that LHRH does not act through cAMP.  相似文献   

15.
Radioimmunoassay technique for measuring 5α,7α-dihydroxy-11-keto-tetranorprosta-1,16-dioic acid, the main urinary metabolite of PGF1α and PGF2α (PGF2α-MUM), was further improved.It was postulated based on some experimental data that the PGF2α-MUM exists in the urine mostly as dioic acid form, not as δ-lactone formThe daily excretion of PGF2α-MUM in men ranged from 14.43 μg to 36.14 μg and in women from 5.21 μg to 14.25 μg.  相似文献   

16.
We studied the prostaglandin (PG) synthetic capacity of microsomes of a relatively pure population of rabbit enterocytes and determined ideal conditions for product synthesis. The epithelial cells were freed from the basement membrane by a combination of calcium chelation and mechanical vibration, and 100,000 x g microsomes were prepared. These microsomes were found to synthesize PG from exogenously added arachidonic acid. The ideal conditions for the reaction were a microsomal protein concentration of 1.0 mg/ml, an arachidonic acid concentration of 33 μM, a reaction mixture pH of 8.0 − 9.5 and with epinephrine 1.5 mM added as a cofactor. The product yields increased linearly with time up to 30 min, of incubation and were inhibited by 100 μM indomethacin. Under the above ideal conditions enterocyte microsomes yielded the following products expressed as pmole/mg protein/20 min, incubation: PGF 98±7, PGE2 48±9, PGD2 28±7, TxB2 40±5, 6 Keto PGF 15 ± 6.  相似文献   

17.
The effect of 13-hydroperoxyoctadecadienoic acid (13-HPODE), a hydroperoxy adduct of linoleic acid (LA), on the activities of prostaglandin (PG) synthesizing and catabolizing enzymes in rabbit gastric antral mucosa was examined. 13-HPODE had no effect on the synthesis of PGE2, PGF and PGD2 from exogenous arachidonic acid in the microsomal fraction of the gastric mucosa at concentrations ranging from 5–20 μM. On the other hand, at 1–10 μM, it inhibited the activity of 15-hydroxy PG dehydrogenase (PGDH), which catalyzes the initial step of catabolism of PGs, in a dose-dependent manner. The concentration required for 50% inhibition was approximately 1 μM. Experiments utilizing LA, 13-hydroxyoctadecadienoic acid and Fe2+ indicated the requirement of the hydroperoxy moiety for the inhibitory effect of 13-HPODE on the PGDH activity. These results suggest that 13-HPODE has the potential to increase the levels of biologically active PGs in gastric mucosa by preventing their inactivation and may have functional effects within the stomach.  相似文献   

18.
The mechanism of stimulatory and inhibitory action of PGF on ovarian steroidogenesis both under and conditions has been studied in the pseudo-pregnant rabbits. Short term incubation of the ovaries with PGF (2.82 × 10−5M) resulted in an increased synthesis of progesterone and 20α-OH P. The addition of PGF in the medium and further incubation of the ovaries obtained from rabbits that had been constantly infused with PGF (0.5 μg/min.) for two hours resulted in increased synthesis of these progestins. The ratio of progesterone to 20α -OH P was also enhanced under these conditions and thus supported the luteotropic action of small doses of PGF under short term incubations. However, as the amount of PGF infused was increased to 5 μg/min., the addition of PGF under conditions strikingly decreased the production of these progestins. The ratio of progesterone to 20α -OH P was also decreased and thus was indicative of luteolytic action of higher doses of PGF. High doses of PGF (5.64 × 10−4M) failed to I cause any significant change in the progestin synthesis under short term incubation. These results thus suggest that the luteotropic and luteolytic action of PGF in the luteinized rabbit ovary is dose and time dependent.  相似文献   

19.
The synthesis of prostaglandins by rheumatoid synovial tissue in organ culture was studied utilizing radioimmunoassay, with antisera to PGB1, PGF and PGF. It was established that PGE2 and PGF were the major prostaglandins formed by analyses of culture media with the two antisera to PGF, before and after alkali treatment. Indomethacin at 5 μg/ml suppressed prostaglandin synthesis, usually to <1% of control cultures. Colchicine, 0.1 μg/ml resulted in marked stimulation of prostaglandin synthesis, in some cases over 10 fold. It is suggested, because of the colchicine effect, that the state of the microtubules may regulate the rate of prostaglandin biosynthesis. It is possible that prostaglandin E2 produced by rheumatoid synovia may contribute to the pathogenesis of the inflammatory reaction and lead to destruction of juxta-articular bone in rheumatoid arthritis.  相似文献   

20.
In rat luteal cells labeled with (3H]oleic acid, PGF-stimulated phospholipase D (PLD) activation was investigated. The PLD activity was detected by measuring the accumulation of [3H]phosphatidylethanol (PtdEt) in the presence of ethanol. PGF stimulated PtdEt accumulation at concentrations of more than 100 nM in the presence of ethanol. However, PtdEt accumulation did not change in the absence of ethanol. PGF (1 μM) increased PtdEt accumulation after 1 min, and the accumulation reached a plateau by 2–3 min. These results indicate that PGF activates PLD in rat luteal cells. U-73122, a phospholipase C (PLC) inhibitor, and staurosporine, a protein kinase C (PKC) inhibitor, did not inhibit PGF-stimulated [3H]PtdEt accumulation. These results suggest that PGF-induced PLD activation is different from PLC-PKC systems. We reported previously that PGF stimulated the release of arachidonic acid. The effects of indomethacin, nordihydroguaiaretic acid (NDGA), and 5,8,11,14-eicosatetraynoic acid (ETYA), inhibitors of arachidonic acid metabolism, on PGF-stimulated PtdEt accumulation were examined. Pretreatment with indomethacin enhanced PGF-induced PtdEt accumulation. In contrast, pretreatment with NDGA and ETYA inhibited PGF-induced PtdEt accumulation. It is suggested that PGF-stimulated PLD activation is mediated via lipoxygenase products.  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号