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 15 毫秒
1.
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   

2.
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   

3.
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   

4.
The inotropic and chronotropic actions of prostaglandin (PG) types PGE1, PGA1, and PGF were studied in isolated guinea pig right and left atria, and papillary muscles; rabbit atria; and toad ventricular strips in order to more completely define the cardiac contractile properties of PG. All three prostaglandins, in muscle bath concentrations of 10μg/ml, exerted positive inotropic and chronotropic actions on guinea pig atrium. These contractile effects were persistent after removal of PG from the muscle bath and appeared to limit the relative response to a subsequent dose of PG. The inotropic action of PGE1 was present over a wide range of bath calcium concentrations (1.1 to 4.4 mM/L). Beta adrenergic receptor blockade, histamine blockade, and pretreatment with reserpine failed to significantly affect the inotropic actions of PG. Norepinephrine and histamine produced more potent inotropic and chronotropic effects on guinea pig atria than did PG and these contractile effects did not exhibit persistence or tachyphylaxis. The prostaglandins did not significantly affect dose response curves for norepinephrine inotropic and chronotropic actions. The prostaglandins had no effect on the force or frequency of contraction in rabbit atria. PGE1 exerted a positive inotropic effect on toad ventricular myocardium whereas PGA1 had no effect and PGF had a negative inotropic action.  相似文献   

5.
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   

6.
The inotropic responses to prostaglandins (PG) A1, E1, E2 and F were studied in isolated cat myocardial tissue. PGA1 and F exhibited no significant inotropic effects, whereas, PGE2 and PGE1 produced negative inotropic effects at concentrations of 2.8 × 10−7 and 2.8 × 10−6 M in isolated cat papillary muscles.In isolated perfused cat hearts, PGE1 (2.8 × 10−6M) produced a negative inotropic effect along with a significant increase in coronary flow. As flow declined, the negative inotropic effect became more severe. PGE1 at 2.8 × 10−9 M produced a sustained increase in coronary flow and oxygen consumption with no inotropic effect. PGE2 and F did not exert significant changes in coronary flow or contractile force.Thus prostaglandins do not appear to exert significant positive inotropic effects at physiologic or at generally accepted pharmacologic concentrations in isolated cat heart preparations. At extremely high concentrations, prostaglandins E1 and E2 exert a negative inotropic effect; however, this would not explain the protective effect of these prostaglandins in circulatory shock.  相似文献   

7.
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   

8.
The effect of prostaglandin E2 (PGE2) on fibroblast proliferation was examined. The presence of PGE2 for 24 h inhibited the growth of quiescent cells stimulated with serum, platelet-derived growth factor and macrophage-derived factors. Maximal inhibition of nuclear labeling with [3H]thymidine occurred at concentrations greater than 10−7 M. The inhibitory effect of PGE2 was less potent in exponentially growing cells and was not the result of conversion of PGE2 to PGA2 during incubation in growth medium. The G1 phase was determined to be 12–14 h in untreated cultures. The extent of growth inhibition by PGE2 was similar with addition of PGE2 at 0, 3, 6, or 9 h following restimulation of quiescent cell cultures. Approximately 25% of the cells that enter S phase are refractory to PGE2-induced growth inhibition. Short-term exposure to PGE2 (5 min and 30 min) caused substantial growth inhibition. The serum-induced proliferation was also inhibited by the cAMP analogue, dibutyrl cAMP. Our results suggest that PGE2 affects a distinct subpopulation of cells. Restimulation of quiescent cells treated with PGE2 for 24 h, indicated that release from PGE2 exposure is associated with prolongation of the G1 phase of the cell cycle.  相似文献   

9.
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   

10.
The effect of oral prostaglandin E2 (PGE2) on gastric acid secretion was examined in healthy subjects. The gastic secretion was stimulated by a modified shamfeeding procedure. Each subject underwent one control test and three tests with intragastrically administered graded doses of PGE2: 0.5, 1.0 and 2.0 mg.Oral PGE2 significantly suppressed the peak and total acid response to vagal stimulation. The total acid output in controls was 27.5 ± 3.2 mol/90 min and 20.8 ± 2.8, 15.8 ± 2.2 (p<0.01) and 15.9±3.8 (p<0.005)mol/90 min in test series with 0.5, 1.0 and 2.0 mg PGE2 respectively. The two higher doses were equally inhibitory to an average 40%. Gastric outputs on sodium and potassium in response to modified shamfeeding were reduced by PGE2.In controls there was a significant release of plasma-gastrin in response to shamfeeding. Plasma-gastrin was apparently suppressed after the two lower doses of PGE2 but 2.0 mg PGE2 gave an elevation similar to controls.Thus the study demonstrates that the oral natural PGE2 suppresses the gastric acid secretion in man. The absence of such an effect in prior studies has been one of the objections against an acid regulatory action of endogenously formed prostaglandins. The present results do not support this argument.  相似文献   

11.
Numerous biochemical pathways influence the synthesis and release of anterior pituitary hormones. Releasing factors extracted from the hypothalamus and prostaglandins (PGs) appear to alter a common biochemical activity, adenyl cyclase, in pituitary cells. Luteinizing hormone releasing hormone (LRH), prostaglandin (PGE1), 7 oxa-13-prostynoic acid and cycloheximide were tested for individual and interacting effects on the in vitro release of FSH, LH and prolactin from hemipituitaries of 15 day old female rats. LRH (10 ng/ml) consistently released both LH and FSH in all in vitro experiments and inhibited prolactin release in 1 of 2 experiments. Lower concentrations (5 and 1 ng/ml) also stimulated LH and FSH release but did not influence prolactin release. Concurrent depletion of stored LH and FSH in the gland was observed. PGE1 in a 6.5 hour incubation increased the storage of LH within the gland in the absence of LRH. In a 1.5 hour incubation in the presence of LRH, storage of LH was also increased. PGE1 had no effect on LH and FSH release; however, in 1 of 2 experiments it stimulated prolactin release in the absence of LRH. Prostynoic acid stimulated LH and FSH release but did not synergize with LRH action in the same tissue. Cycloheximide did not affect LH release during the first 30 minutes of incubation; however, the release during the subsequent 1 hour was significantly inhibited. Similar tissue also exposed to cycloheximide was still responsive to LRH during the latter 1 hour incubation period. Cycloheximide had no effect on prolactin storage and release from the same tissue.  相似文献   

12.
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   

13.
The metabolism of PGE2 by extracts of renal cortex is species dependent. In the rat PGE2-15-hydroxydehydrogenase initiates metabolism whereas in the rabbit PGE2-9-ketoreductase predominates. In man both mechanisms may operate. Each of the metabolic enzymes, which limits the vasodilator-diuretic actions of PGE2, was inhibited by ethacrynic acid, furosemide and indomethacin. Some inhibition of PGE2-9-ketoreductase was also observed with chlorthalidone, hydralazine and phentolamine but the thiazide diuretics and a number of other cardiovascular-active agents were without significant effect. We conclude that the inhibition of PGE2-9-ketoreductase and PGE2-15-hydroxydehydrogenase could contribute to the mechanism of action of the non-thiazide diuretics in man.  相似文献   

14.
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   

15.
Viprostol, a novel prostaglandin E2 congener, was assessed for antilipolytic activity in the spontaneously obese rat. In isolated epididymal adipocytes, viprostal exhibited a dose-dependent inhibition of catecholamine-stimulated lipolysis at concentrations ranging from 10 μM to 1 mM, but was ineffective at lower concentrations. Additionally, viprostal exhibited approximately 50% of the antilipolytic activity of naturally-occurring PGE1 and PGE2 at similar concentrations, but was as potent as PGF. At 10 μM, viprostol inhibited maximum catecholamine-stimulated lipolysis by approximately 35% of the total, hormone-stimulated glycerol release. The results of these experiments indicate that viprostol exhibits antilipolytic activity , but is less potent than the naturally-occurring PGE's to which it is most closely related structurally.  相似文献   

16.
Radioimmunoassays of platelet prostaglandins E1 and F in platelet rich plasma or platelet suspension, demonstrate that both PGE1 and PGF are present at higher concentrations than prostaglandins E2 and F. Gas chromatography — mass spectrometry determinations of prostaglandins E1 and E2 in resting washed platelets confirm this difference. Lastly, there is a greater incorporation of [1-14C] acetate into prostaglandins E1 and F compared to that into prostaglandins E2 and F.  相似文献   

17.
We studied PGE2 specific binding sites in human myometrial microsomes prepared from uterine specimens obtained by hysterectomy (women between 38 and 55 years of age). Competition experiments showed that the potency order for various prostaglandins (PGs) was : PGE2 ≥ PGE1 PGF > Iloprost ≥ Carbacyclin ZK 110841 (PGD2 analogue). These relative affinities indicated that the receptor was of the EP type.In kinetic experiments GTP, GppNHp and GTPγS increased the rate of PGE2 binding (steady state was reached more rapidly in the presence of nucleotides) but maximal specific binding was not significantly different. Complete dissociation could not be obtained, even in the presence of GTP. Only 50% of maximal binding was readily dissociable. The dissociation rate was 4.56.10−4 sec−1 (half time of about 660 sec) and in the presence of GTP analogues it was slightly increased (k−1 = 7.16 10−4 sec−1 half time 420 sec.). Scatchard analysis of saturation curves showed an increase in ligand receptor affinity in the presence of GTP or nucleotide analogues: the Kd shifted from 9.66 ± 2.8.10−9 M to 4.96 ± 1.25.10−9M, but the number of binding sites did not change significantly (310 ± 37 to 350 ± 17 fmol/mgP). The effect of GTP was observed at a concentration of 5.10−4M. GppNHp and GTPγS were effective at 1.10−5M. Pretreatment of myometrial membranes with pertussis or cholera toxins had no effect on PGE2 binding to membrane sites. Our conclusion is that GTP induced conversion of a population of low affinity sites into a population of higher affinity sites. This effect of guanine nucleotides was described in adipocytes and kidney medulla.Competition studies with PGE2 analogues (sulprostone, 17-phenyl-ω-trinor PGE2, M&B 28,767, misoprostol, butaprost) showed that this receptor mediates a contractile response and is probably an EP3 subtype.  相似文献   

18.
Four prostaglandins-PGE1, PGE2, 190H PGE1 and 190H PGE2-were quantified in human seminal fluid by GC-MS-SIM using only the internal standard, d4-PGE2. Methods and calculations were developed to minize errors inherent in using only one internal standard for quantifying four closely related prostaglandins. Preliminary data concerning the statistical significance of the differences found between PGE and 190H PGE levels in fertile, azospermic and oligospermic men are reported.  相似文献   

19.
The action of prostaglandins and indomethacin on gastric mucosal cyclic nucleotide concentrations was evaluated in 18 anesthetized mongrel dogs. Prostaglandins E1 (PGE1) and E2 (PGE2) (25 μg/kg bolus, then 2 μg/kg/min) were administered both intravenously (4 experiments; femoral vein) and directly into the gastric mucosal circulation (10 experiments; superior mesenteric artery). The possible synergistic effect of pre-treatment and continuous arterial infusion of indomethacin (5 mg/kg bolus for 5 min, then 5 mg/min), a prostaglandin synthetase inhibitor, with PGE2 was studied in 4 experiments. Antral and fundic mucosa were biopsied and measured by radioimmunoassay for cyclic nucleotides. Doses of PGE1 and PGE2 which inhibited histamine-stimulated canine gastric acid secretion did not significantly alter antral or fundic mucosal cyclic nucleotide concentrations. Concomitant infusion of PGE2 with indomethacin did not potentiate the mucosal nucleotide response compared to PGE2 alone. These studies fail to implicate cyclic nucleotides as mediators of the inhibitory acid response induced by PGE1 or PGE2 in intact dog stomach.  相似文献   

20.
The effects of PGE2 and its stable analogue, 16, 16 dimethyl PGE2 (dmPGE2) were investigated on ethanol-induced gastric mucosal haemorrhagic lesions and leukotriene formation in the rat. Exposure of the rat gastric mucosa to ethanol , produced a concentration-related increase in the mucosal formation of leukotriene B4 (LTB4) which was correlated with macroscopically-apparent haemorrhagic damage to the mucosa. Challenge with absolute ethanol likewise enhanced the mucosal formation of LTC4 whereas the mucosal formation of 6-keto-PGF was unaffected. Challenge of the rat gastric mucosa with ethanol induced a concentration-dependent increase in the formation of LTB4 and LTC4, but not 6-keto PGF. Pretreatment with PGE2 (200–500μg/kg p.o.) prevented the haemorrhagic mucosal damage induced by oral administration of absolute ethanol but not the increased formation of leukotrienes by the mucosa. In contrast, pretreatment with a high dose of dmPGE2 (20μg/kg p.o.) prevented both the gastric mucosal lesions and the increase mucosal leukotriene formation. The differences in the effects of these prostaglandins may be related to the nature or degree of protection of the gastric mucosa. Thus, high doses of dmPGE2 but not PGE2 may protect the cells close the luminal surface of the mucosa and hence reduce the stimulation of leukotriene synthesis by these cells.  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