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1.
In these experiments we have examined the effects of PGE1, PGE2, PGF and PGF on synovial perfusion in the normal canine synovial microcirculation. The effects of the drugs on synovial perfusion were determined indirectly from the changes produced in the rate of clearance of 133Xenon from the joint by their intra-articular injection. Prostaglandins PGE1 and PGE2 were found to be strongly vasodilator with PGE1 being the more active. PGF appeared to have little or no vasoactive properties in doses up to 1 ugm. (2.8 × 10−5M) in our I preparation while PGF was vasodilator at this high dosage only. Neither SC19920 nor diphloretin phosphate antagonised the effects of PGE1 in these experiments.  相似文献   

2.
The phenylephrine-stimulated perfused oviduct of the rabbit was evaluated as a model for studying the activity of prostaglandins that produce inhibition of the oviducal smooth muscle. Elevation of the normal “tone” of the oviduct by perfusing phenylephrine through the lumen permitted quantitation of the responses to PGA2, PGE1 and PGE2 by measuring the magnitude of the inhibitory response produced by the agents. PGE2 was relatively more potent, efficacious and specific for the oviduct than PGA2 or PGE1. It was concluded that the model was suitable for comparative dose-response studies of PGA2, PGE1 and PGE2 and their analogs.  相似文献   

3.
The effects of a wide range of PGE1 and PGE2 concentrations on the isometric developed tension of isolated rat atria beating spontaneously or paced at a fixed rate, were explored. PGE1 only produced a negative inotropic effect (NIE), whereas PGE2 elicited a biphasic inotropic action; negative at low concentrations and positive (PIE) at higher ones. Phenoxybenzamine and phentolamine failed to modify either the NIE or the PIE, but subthreshold exogenous norepinephrine abolished the NIE, suggesting a presynaptic inhibitory effect of PGEs on the adrenergic neurotransmitter release. Auricles pretreated with subthreshold norepinephrine react with a PIE to PGE1, but not to PGE2. On the contrary in the presence of subthreshold methoxamine the PIE of PGE2 was increased whereas the action of PGE1 was not modified.  相似文献   

4.
Patterns of arachidonic acid release and metabolism were altered in human synovial fibroblasts following exposure to cytokines. Recombinant interleukin-1 induced an approximate 3-fold in crease in [3H]-AA release, a 7-fold increase in PGE2 production and a 2-fold increase in PLA2 activity in human synovial fibroblasts. Recombinant tumor necrosis factor induced similar responses, however, the magnitude was less than that mediated by interleukin-1. A combination of the two cytokines had an additive effect on [3H]-AA release and PLA2 activity while PGE2 production was similar to that detected using interleukin-1 alone. [3H]-AA, was released in substantial amounts when sodium fluoride was used as a stimulus but PGE2 was not. These data show that tumor necrosis factor and interleukin-1 can both activate synovial cell PLA2 and induce generation of PGE2, but act in an additive rather than a synergistic fashion. Furthermore, the data show that PGE2 production is not always concordant with [3H]-AA release, suggesting that appropriate enzyme(s) must be activated.  相似文献   

5.
Effects of PGE1 or PGE2 on luteal function were studied in 163 pseudopregnant rats. PGE1 (10, 100, or 300μg) given intrauterine every 6 hr did not shorten pseudopregnancy (P < 0.05), however, the same doses of PGE2 given intrauterine every 6 hr advanced luteolysis (P < 0.05). PGE1 (100 or 300μg) given every 4 hr intramuscular maintained levels of progesterone in peripheral blood above controls (P < 0.05) while 100 or 300μg of PGE2 hastened the decline in progesterone (P < 0.05). The antiluteolytic effect of PGE1 was not via an inhibition of PGF secretion (P < 0.05) by the uterus or by induction of ovulation in treated animals. Moreover, PGE1 (100, 200, or 500μg) given intramuscular every 4 hr from day 4 of pseudopregnancy until the next proestrus delayed luteal regression around 3 days (P < 0.05). PGE2 at doses of 100, 200, or 500μg every 4 hr given intramuscular consistently shortened pseudopregnancy (P < 0.05). Lower doses were without effect (P < 0.05). Based on the above data it is concluded that PGE2 is consistently luteolytic whereas PGE1 is not luteolytic in pseudopregnant rats and that PGE1 may be an antiluteolysin.  相似文献   

6.
Several bisdeoxy PGE1 analogs are potent, competitive antagonists of PGE1-induced colonic contractions in the gerbil. The efficacy of these analogs in antagonizing PGE1-mediated systemic vasodepression has not been previously demonstrated. In this study, serial doses of PGs were administered before, during and after infusion of d,1–11, 15-bisdeoxy PGE1. Bolus injections of PGE1 (3.0 μk/kg), PGE2 (3.0 μg/kg) and PGI2 (0.3 μg/kg) were administered via the right external jugular vein to male Wistar rats. PGE1, PGE2 and PGI2 decreased systemic arterial pressure 41%, 38% and 38%, respectively. The PGE1 analog was infused (200 μg/kg/min) through the right common carotid artery. The analog itself had no effect on mean systemic arterial pressure, but maximum reversible inhibition (51%) of PGE1-mediated vasodepression occurred following a 50 minute infusion. No significant effect of the PGE1 analog was observed on PGE2 or PGI2-mediated vasodepression. These data demonstrate the ability to antagonize PGE1-mediated vasodepression, and to differentiate the vascular responses to PGE1 and PGE2 or PGI2.  相似文献   

7.
Prostaglandin (PG) biosynthesis by trypsin-dispersed cat adrenocortical cells was studied by radioimmunoassay (RIA). Parallel assays of incubation media using PGF and PGF antisera established that PGF is the primary PGF released by feline cortical cells. Following the reduction of PGE to PGF with sodium borohydride (NaBH4) these same two antisera were also used to identify PGE2 as the primary PGE released. RIA using a PGE antiserum confirmed the presence of PGE in the incubation medium. Steroidogenic concentrations of ACTH (50–250μU) enhanced PGE and PGF release, and indomethacin suppressed the ACTH-facilitated release. These studies provide additional evidence for ACTH-induced PG synthesis by feline cortical cells, and support the hypothesis that PGs play some role in the steroidogenic action of ACTH.  相似文献   

8.
The objective of this study was to determine whether prostaglandin E1 (PGE1) or prostaglandin E2 (PGE2) prevents premature luteolysis in ewes when progesterone is given during the first 6 days of the estrous cycle. Progesterone (3 mg in oil, im) given twice daily from Days 1 to 6 (estrus = Day 0) in ewes decreased (P < 0.05) luteal weights on Day 10 postestrus. Plasma progesterone concentrations differed (P < 0.05) among the treatment groups; toward the end of the experimental period, concentrations in jugular venous blood decreased (P < 0.05) compared with the other treatment groups. Plasma progesterone concentrations in ewes receiving PGE1 or PGE1 + progesterone were greater (P < 0.05) than in vehicle controls or in ewes receiving PGE2 or PGE2 or PGE2 + progesterone. Chronic intrauterine treatment with PGE1 or PGE2 prevented (P < 0.05) decreases in plasma progesterone concentrations, luteal weights, and the proportion of luteal unoccupied and occupied LH receptors on Day 10 postestrus in ewes given exogenous progesterone, but did not affect (P > 0.05) concentrations of PGF in inferior vena cava blood. Progesterone given on Days 1 to 6 in ewes advanced (P < 0.05) increases in PGF in inferior vena cava blood. We concluded that PGE1 or PGE2 prevented progesterone-induced premature luteolysis by suppressing loss of luteal LH receptors (both unoccupied and occupied).  相似文献   

9.
The prostaglandin endoperoxide PGH2, HHT, HETE, thromboxane A2, and thromboxane B2, which are all products of arachidonic acid metabolites of human platelets, were tested for their ability to modulate platelet cyclic nucleotide levels. None of the compounds tested altered the basal level of cAMP or cGMP, and only PGH2 and thromboxane A2 inhibited PGE1-stimulated cAMP accumulation. Thromboxane A2 was found to be a more potent inhibitor of PGE1-stimulated cAMP accumulation and inducer of platelet aggregation thatn PHG2.  相似文献   

10.
The vasoconstrictor effects of PGE2 and PGF are less pronounced on retinal vessels of the newborn than of the adult pig. We tested the hypothesis that the decreased vasomotor response to these prostaglandins might be due to relatively fewer receptors and/or different receptor subtypes (in the case of PGE2) on retinal vessels of the newborn animal. Binding studies using [3H]PGE2 and [3H]PGF revealed that PGE2 (EP) and PGF (FP) receptor densities in retinal microvessel membrane preparations from newborn animals were approximately 25% of those found in vessels from the adult. The Kd for PGF did not differ; however, the Kd for PGE2 was less in newborn than in adult vessels. Competition binding studies using AH 6809 (EP1 antagonist), butaprost (EP2 agonist), M&B 28,767 (EP3 agonist), and AH 23848B (EP4 antagonist) suggested that the retinal vessels of the newborn contained approximately equal number of EP1 and EP2 receptor subtypes whereas the main receptor subtype in the adult vessels was EP1. In addition, PGE2 and butaprost produced comparable increases in adenosine 3′,5′-cyclic monophosphate synthesis in newborn and adult vessels. PGE2, 17-phenyl trinor PGE2 (EP1agonist) and PGF caused a 2.5 to 3-fold greater increase in inositol1,4,5-triphosphate (IP3) formation in adult than in newborn preparations. It is concluded that fewer PGF receptors and an associated decrease in receptor-coupled IP3 formation in the retinal vessels of the newborn could lead to weaker vasoconstrictor effects of PGF on retinal vessels of the newborn than of adult pigs; fewer EP1 receptors (associated with vasoconstriction) and a relatively greater proportion of EP2 receptors (associated with vasodilation) might be responsible for the reduced retinal vasoconstrictor effects of PGE2 in the newborn.  相似文献   

11.
Prostaglandins are well known for their ability to stimulate contraction in gastrointestinal smooth muscle, yet very little information is available on how their activity affects propulsion . Thus, studies were undertaken to determine the effect of various prostaglandins on qastric emptying (GE) and small intestinal transit (SIT) in unanesthetized fasted rats. Rats were treated with intravenous, subcutaneous, or oral PGF2α, PGE2, or 16,16 dimethyl PGE2 at various doses, followed 1 (intravenous), 20 (subcutaneous) or 10 (oral) mins later by intragastric 51Cr oxide in black ink. Forty-five mins later, rats were sacrificed by CO2 asphyxiation, the pylorus clamped, and the gut excised. SIT was expressed as the percent of intestinal length traveled by the most distal portion of ink. GE was expressed as the percent of the 51Cr emptied into the intestines. If GE was affected by prostaglandin treatment, the experiments were repeated with rats pre-implanted with duodenal cannula. This preparation allowed the visual transit marker to be deposited directly into the dueodenum, thus avoiding acceleration or delay of SIT caused by fluctuations in GE. The results of these studies show that: (1) intravenous 16,16 dimethyl PGE2 (5–50 μg/kg), but not PGF2α or PGE2, accelerates GE and delays SIT; (2) oral prostaglandin administration increases SIT; (3) oral 16,16 dimethyl PGE2 delays GE; (4) subcutaneous 16,16 dimethyl PGE2 accelerates, has no effect upon, or delays GE depending upon dose, but accelerates SIT at all doses tested; and (5) subcutaneous PGE2 accelerates SIT while PGF2α does not. Thus, the effect of prostaglandins on GE and SIT depends upon the dosage and route of administration as well as type of prostaglandin used.  相似文献   

12.
A method for quantification of 6-keto-PGF, 2,3-dinor-6-keto-PGF, TXB2, 2,3-dinor TXB2, PGE2, PGD2 and PGF in human urine samples, using gas chromatography—negative ion chemical ionization mass spectrometry, is described. Deuterated analogues were used as internal standards. Methoximation was carried out in urine samples which were subsequently applied to phenylboronic acid cartridges, reversed-phase cartridges and thin-layer chromatography. The eluents were further derivatized to pentafluorobenzyl ester trimethylsilyl ethers for final quantification by gas chromatography—mass spectrometry. The overall recovery was 77% for tritiated 6-keto-PGF and 55% for tritiated TXB2. Urinary levels of prostanoids were determined in a group of six volunteers before and after intake of the thromboxane synthase inhibitor Ridogrel, and related to creatinine clearance.  相似文献   

13.
It is known that PGE2 is a potent stimulus of LH release. To determine if the effect of PGE2 could be enhanced and/or prolonged by retarding its metabolic degradation, a derivative, 15-methyl PGE2 (15-E2) which is more slowly degraded than the natural compound was injected intravenously (i.v.) at various dose levels or into the third ventricle (3rd V) of ether-anesthetized, ovariectomized, estrogen (OVX, Eb)-treated rats and its effect on gonadotropin release was compared with that of PGE2. Both PGs injected i.v. were equally effective in increasing plasma LH and maintaining the elevated levels, although 15-E2 induced a larger and more sustained increase in plasma FSH than PGE2. By contrast, 3rd V PGE2 was clearly more effective than 3rd V 15-E2 in releasing LH and to a lesser extent, FSH. The effect of 15-E2 on LH was similar to that produced by 3rd V PGE1 injected at a similar dose. However, its effect on FSH was greater than that of PGE1.To evaluate the effect(s) of prostaglandins of the A and B series on gonadotropin release, PGA1, PGA2, PGB1 or PGB2 were injected intraventricularly in OVX, Eb-treated rats. PGBs were injected into conscious, free-moving rats. PGA2 or PGB2 increased plasma LH concnetrations although much less effectively than PGE2. Third V PGA1 or PGB1 were ineffective. The 3rd V injection of two cyclic esters (U-44069 and U-46619), stable analogs of the PG endoperoxide PGG2 and PGH2, induced a small, transient increase in LH levels and did not alter plasma FSH in conscious, free-moving animals. PGE2 injected intraventricularly at a similar dose was demonstrated to be much more potent than the analogs in stimulating LH and FSH release. The results indicate that: 1) 15-E2, in spite of its described long-lasting activity, does not appear to be more potent than the natural compound in releasing LH, although when injected i.v., it appeared to induce a more sustained increase in plasma FSH; 2) although PGA2 and PGB2 can also act centrally to stimulate LH release, their low potency suggests that this is a pharmacological effect; and 3) the two analogs of PG endoperoxides tested proved to be poor stimuli for gonadotropin release. The significance of these findings is discussed.  相似文献   

14.
Sulprostone is a tissue-specific PGE2-derivative with high abortifacient activity in various species including man. The dissociation constant KD of the receptor binding of this compound was compared with PGE2 and PGF in various tissue preparations of different species. A structure-binding relationship was developed from competition curves after a logit/log transformation. It is demonstrated that the relative affinities of Sulprostone, PGE2 and PGF remain essentially constant in all the tissues investigated. It is concluded that the tissue-specificity of Sulprostone cannot be ascribed to structural differences of the receptor molecule.  相似文献   

15.
Intracerebroventricular administration of prostaglandins E1 or E2 was shown to block, while PGF increased the incidence of tonic convulsion due to electroshock in mice. The Prostaglandins were administered intracerebroventricularly (i.c.v.) to conscious mice by a modification of Haley and McCormick's method (1) prior to a transcorneal maximal electroshock (MES) or a transcorneal supra-maximal electroshock (SMES). PGE1 and PGE2 i.c.v. blocked the tonic hindlimb extension (THE) and protected the animals from death induced by MES with ED50's for PGE1 and PGE2 for inhibition of the THE of 6.6 (4.3–12.0) μg/mouse i.c.v. and 13.3 (8.9–22.4) μg/mouse i.c.v. respectively. When PGE2 was administered intraperitoneally (i.p.) in doses as high as 4.0 mg/kg it did not block the THE. However, the duration of the THE as well as the mortality were reduced by doses of 0.5–4.0 mg/kg PGE2 i.p.. Both PGE1 and PGE2 were shown to cause a dose related significant (p<.001) decrease in the duration of the THE with SMES in doses of 1–10 μg/mouse i.c.v. for PGE1 and 2–40 μg/mouse i.c.v. for PGE2. PGF, administered i.c.v. prior to a transcorneal electroshock equivalent to a current at the ED1 level, increased the incidence of the THE as well as the mortality in doses of 20–50 μg/mouse.  相似文献   

16.
We have investigated the direct effects of prostaglandins E1, E2, F and D2 on renin release from rabbit renal cortical slices. Prostaglandin E1 (PGE1) was the most potent stimulant of renin release, while PGE2 was 20–30 fold less active. PGF was found not to be an inhibitor of renin release as reported by others, but rather a weak agonist. PGD2 up to a concentration of 10 μg/ml had no activity in this system. That the stimulation of renin release by PGE1 is a direct effect is supported by the finding that PGE1-induced release is not blocked by L-propranolol or by Δ5,8,11,14-eicosatetraynoic acid (ETYA), a prostaglandin synthesis is inhibitor. The fatty acid precursor of PGE1, Δ8,11,14-eicosatrienoic acid, also stimulated renin release, an effect which was blocked by ETYA. In addition to the above findings, ethanol, a compound frequently used to dissolve prostaglandins, was shown to inhibit renin release.  相似文献   

17.
To determine the release and absorption profile of prostaglandin E2 from a new vaginal film formulation containing 850 μg PGE2, serial plasma levels of 13,14-dihydro-15-keto PGE2 were measured by radioimmunoassay in pregnant women between 16 and 18 weeks gestation. A control group, using placebo vaginal film was included in the study. There was a somewhat uniform increase in the plasma levels of the PGE2 metabolite, reaching peak levels between 4 and 6 hours after application of the film. The findings suggest that this drug formulation could be used clinically when slow constant release of the prostaglandin is required over a period of hours such as in pre-induction cervical ripening of term pregnancy.  相似文献   

18.
The interaction between interleukin IL-1α and PGE2 on P388D2 on cells has been investigated. Preincubation of murine macrophage-like cells, P388D1, with IL-1α (0–73 pM) reduced the binding of PGE2 to these cells in a concentration-dependent manner. Scatchard analysis showed that IL-1α decreased the PGE2 binding by lowering both the high and low affinity receptor binding capacities (from 0.31 ± 0.02 to 0.12 ± 0.01 fmol/106 cells for the high affinity receptor binding sites and from 2.41 ± 0.12 to 1.51 ± 0.21 fmol/106 cells for the low affinity receptor binding sites). However, the dissociation constants of the receptor of the IL-1α-treated cells remained unchanged. Inhibition of PGE2 binding IL-1α did not involve changes in either protein phosphorylation or intracellular cyclic AMP levels. Our data clearly show that IL-1α inhibits the binding of PGE2 to monocytes/macrophages and may thereby counter the immunosuppressive actions of PGE2.  相似文献   

19.
MDL-646, 11,15-dihydroxy-16-methyl-16-methoxy-9-oxo-prost-13-en-1--oic acid methyl ester, is one of the most active members of a new class of PGE1 analogues with potent gastric cytoprotective and antisecretory activity. The potential luteolytic activities of MDL-646 and its corresponding PGE2 derivative, L 14224 were assessed from their ability to terminated pregnancy and to reduce plasma progesterone levels in the hamster. PGE1 and PGE2 were used as reference compounds. The biological and biochemical data clearly demonstrate that these 16-methyl-16-methoxy PGE derivatives, given s.c. or p.o. either once or for 3 days, have no luteolytic effects up to a daily dose of 2–2.5 mg/kg, and are therefore at most to as luteolytic as the parent natural PGEs. The dissociation between gastroprotective and luteolytic activity was interpreted to indicate that these new PGE derivatives have a specific action.  相似文献   

20.
Prostaglandins PGE1 and PGE2 extracted from bovine semen, purified via silicic column chromatography were quantified by gas chromatography as their methoxime methyl ester trimethylsilyl ether derivatives. The PGE1 and PGE2 concentrations of 19 bovine semen samples ranged from 395 ± 225 and 487 ± 407 ng/ml, respectively. A constant 1:1 ratio between PGE1 and PGE2 was observed. There was no relationship between PGE and sperm motility, but high sperm counts were apparently associated with decreased PGE levels. The direct precursors of PGE1 and PGE2, i.e. 20:3n6 and 20:4n6, occurred in low concentrations compared to other related unsaturated fatty acids, i.e. 18:2n6 and 22:5n6 of the n-6 family.  相似文献   

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