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1.
The effects of thyroxine (T4) and methimazole administration on plasma prostacyclin (PGI2) levels in vivo and on PGI2 release by aortic rings incubated in vitro were investigated in rats. Male rats were given single injection of T4 (200 μg/100 g body wt) ip every 24 h for either 3, 7 or 14 days for hyperthyroid rats. For hypothyroid rats, a group of rats were given methimazole (0.01 % in drinking water) for 14 days. PGI2 concentrations were determined in plasma and also in the medium in which aortic rings were incubated. PGI2 was measured as 6-keto-PGF1α by RIA. Plasma PGI2 levels in T4-treated groups were found to be significantly higher than those of control animals. Aortic rings obtained from rats given single injection of T4 for 7 and 14 days showed significant increases in release of PGI2 into the incubation medium. In contrast, rats given methimazole for 14 days showed a significant decrease in the production of PGI2 by aortic rings without any significant changes in plasma levels. Direct addition of T4 into the incubation medium did not cause any significant changes in PGI2 release by aortic rings obtained from control rats.These results suggest the regulatory role of thyroid hormone in PGI2 synthesis in vivo.  相似文献   

2.
The effects of estradiol and testosterone on prostacyclin (PGI2) release (measured as 6-keto-PGF1 alpha) by vascular tissues using rat aortic rings and cultured rabbit aortic smooth muscle cells (SMC) were investigated. Aortic SMC were prepared from either explants of atherosclerotic intima or those of normal media. Aortic rings obtained from male and female rats which had been treated with estradiol resulted in increased PGI2 synthesis. Furthermore, PGI2 synthesis by cultured medial SMC was significantly increased in the presence of estradiol (10(-7), 10(-9) M). An increased tendency in PGI2 synthesis was also observed in intimal SMC. On the other hand, aortic rings obtained from female rats treated with testosterone resulted in a significant decrease in PGI2 synthesis. However, aortic rings from testosterone-treated male rats and cultured medial and intimal SMC treated with testosterone (10(-6), 10(-8) M) for 48 hr did not show any significant changes in PGI2 synthesis. We also found greater PGI2 synthesis by intimal SMC compared with that by medial SMC. These results suggest that estradiol and testosterone may have opposite functions in the development of atherosclerosis, that is, estradiol for anti-atherosclerotic and testosterone for atherogenic, by modulating PGI2 synthesis by vascular tissues.  相似文献   

3.
Continuously superfused rat anterior pituitary cells were used to study the effects of exogenous prostaglandins (PGs) and thromboxanes (TXs) on the secretion of prolactin (PRL). No change in hormone release was observed upon superfusion with TXB2 (10(-5)M) or the TX synthesis inhibitor, imidazole (1.5 mM). PGs A2, B2, D2, E1, E2, F1 alpha, F2 alpha, and endoperoxide analogs, U-44069 and U-46619, also had no effect on PRL secretion (all at 10(-5)M). In contrast 10(-5)M PGI2 was repeatedly found to stimulate PRL release to a level at least 125% above control, while producing no apparent change in the amount of hormone secreted in response to TRH. Somatostatin (SRIF), at a dose of 10(-6)M, maximally inhibited TRH-induced PRL output, but failed to alter the PRL response to PGI2. These studies indicate that PGI2 may have a direct effect on the anterior pituitary to modify PRL secretion.  相似文献   

4.
Physiological roles have been suggested for prostacyclin in the cardiovascular system. Prostacyclin was administered by intravenous infusion to unanesthetized rats. Over a 24 hr period, 0.32 mg/kg/day caused only flushing of the ears. Larger doses (0.56 and 1 mg/kg/day) caused hypothermia, behavioral depression, and swelling of the paws. Cumulative dose-response curves for its depressor action were determined in both unanesthetized and anesthetized, vagotomized, ganglion-blocked rats. In unanesthetized rats, the threshold dose was about 0.1 ug/kg/min. Respiratory depression precluded doses larger than 1 ug/kg/min. In anesthetized rats, the threshold dose was about 0.001 ug/kg/min, and the maximally effective dose was about 0.1 micrograms/kg/min. At 0.032 ug/kg/min, blood pressure first fell and then rose slightly. This compensatory rise did not occur in nephrectomized rats, suggesting renin release as the mechanism. Intravenous infusion of 0.1 but not 0.01 ug/kg/min in unanesthetized rats doubled plasma renin activity. In saline-loaded unanesthetized rats, urine volume and urinary sodium excretion were decreased by 0.1 ug/kg/min of prostacyclin.  相似文献   

5.
In the rat paw prostacyclin was 5--10 times less potent than PGE2 in causing oedema, and 5 times less potent in potentiating carrageenin-induced oedema, which it did in a dose-related manner. Prostacyclin was 5 times more potent than PGE2 in producing hyperalgesia and as potent as PGE2 in restoring carrageenin-induced hyperalgesia. The effects on oedema were longer lasting than those on hyperalgesia. 6-oxo-PGF1alpha was 500 times less potent than PGE2 in causing oedema by itself and in potentiating carrageenin-induced oedema. It had no hyperalgesic activity in this test.  相似文献   

6.
Using strips of rat pregnant uterus, treated with indomethacin to suppress spontaneous contractility, the oxytocic activity of prostacyclin was compared with other prostaglandins. A prostacyclin concentration of 32 ng/ml elicited uterine contractions in all experiments. In this respect prostacyclin was 80 times more active than 6-oxo-PGF1 alpha but less active than PGE2 or PGF2 alpha. Apart from a direct stimulant effect, prostacyclin also exhibited an indirect potentiating action. In threshold concentrations prostacyclin caused a 3-fold potentiation of threshold doses of oxytocin. A lesser 1.5-fold potentiation of PGE2 alpha was also observed. The implications of these findings in relation to prostacyclin playing a role in parturition are discussed.  相似文献   

7.
The effects of prostacyclin (PGI2) and its stable metabolite 6-oxo-PGF1alpha on various bioassay tissues are compared with those of PGE2 and PGF2alpha, using the cascade superfusion method. On vascular smooth muscle, PGI2 caused relaxation of all tissues tested except the rabbit aorta. PGE2 relaxed rabbit coeliac and mesenteric artery but contracted bovine coronary artery and had no effect on rabbit aorta. 6-oxo-PGF1alpha was ineffective at the concentrations tested. On gastro-intestinal smooth muscle, PGI2 contracted strips of rat and hamster stomach and the chick rectum. It was less potent than PGE2 or PGF2alpha. None of these substances contracted the cat terminal ileum. 6-oxo-PGF1alpha was inactive on these tissues at the doses tested. PGI2 was less active than PGE2 or PGF2alpha in contracting guinea-pig trachea and rat uterus; 6-oxo-PGF1alpha was active only on the rat uterus. Thus, PGI2 can be distinguished from the other stable prostaglandins using the cascade method of superfusion.  相似文献   

8.
We explored the possibility that prostacyclin might be the dilator metabolite of postprandial hyperemia. In canine free-flow preparations, effects of prostacyclin were compared with effects of actively absorbed nutrients on hemodynamic and metabolic parameters in the small intestine. Prostacyclin was infused directly into the superior mesenteric artery for 10 minutes at 1.0 nanograms/kg-min. In absorptive study an isosmotic solution of glucose (1.0 g/l) dissolved in 0.9% NaCl was perfused through the gut lumen for 20 minutes. Prostacyclin increased total blood flow to the intestinal segment and decreased oxygen extraction, while not significantly changing either oxygen consumption or PS-product. Active cotransport of glucose and sodium increased total blood flow, oxygen extraction, oxygen consumption and PS-product.In constant flow canine gut preparations, intraarterial prostacyclin infusion decreased arterial pressure, oxygen extraction, oxygen consumption and mesenteric vascular resistance but increased venous pressure. Absorption of glucose and sodium increased oxygen extraction but decreased mesenteric vascular resistance while not affecting other parameters significantly.Since responses to prostacyclin did not coincide with responses to metabolically dependent transport of glucose and sodium, we conclude that the dilator metabolite of postprandial hyperemia is probably not prostacyclin.  相似文献   

9.
10.
Release of PGI2 by slices of muscularis and mucosa layers of rat corpus stomach was investigated. An anti-aggregatory substance that was released by slices of muscularis was identified as PGI2 in various bioassay systems including anti-serum against PGI2 as well as by stimulation of its generation with AA or PGH2 and by inhibition of this generation with indomethacin or tranylcypromine, respectively. PGI2 was the major PGs released from slices of muscularis. The release of PGI2 from muscularis surpasses a similar release of PGI2 from mucosa by a factor of 10. On the other hand, degradation of exogenous PGI2 was 4 times faster by mucosa than by muscularis slices. Our conclusion is that in the stomach corpus wall of rats, muscularis is the main source of PGI2, which may play a role in regulation of mucosal blood flow.  相似文献   

11.
Metabolism of prostacyclin, [9-3H]PGI2, was examined in the isolated perfused rabbit lung and the post-microsomal supernate of rabbit lung homogenate. Two major metabolites of [9-3H]PGI2 from the lung perfusate were separated by thin-layer chromatography and radiometric gas-chromatography. These two products were identified as 6 keto-PGF and 6,15 diketo-13,14 dihydro PGF by mass-spectrometry; they represented 65% and 14% of the total radioactivity. When [9-3H]PGI2 was incubated with the lung homogenate in the presence of either NAD+ or NADP+, more than 36% and 25%, respectively, was converted to the 6,15 diketo-13,14 dihydro metabolite.  相似文献   

12.
Injections of 1 mg PGI2 directly into the bovine corpus luteum significantly increased peripheral plasma progesterone concentrations within 5 min. Concentrations were higher in the PGI2-treated heifers than in saline-injected controls between 5 and 150 min and at 3.5, 4, 5, and 7 h post-treatment. Levels tended to remain elevated through 14 h. Saline and 6-keto-PGF1 alpha were without effect on plasma progesterone levels. The luteotrophic effect of PGI2 was not due to alterations in circulating LH concentrations. An in vitro experiment assessed the effects of either PGI2 alone or in combination with LH on progesterone production by dispersed luteal cells. Progesterone accumulation over 2 h for control, 5 ng LH, 1 microgram PGI2, 10 micrograms PGI2, and 10 micrograms PGI2 plus 5 ng LH averaged 99 +/- 42, 353 +/- 70, 152 +/- 35, 252 +/- 45, and 287 +/- 66 ng/ml (n = 4), respectively. Thus PGI2 has luteotrophic effects on the bovine CL both in vivo and in vitro.  相似文献   

13.
Dietary nucleotides affect the maintenance of immune responses, tissue repair and polyunsaturated fatty acid metabolism. Orotate, a pyrimidine nucleotide precursor, induces fatty livers by impairing VLDL hepatic secretion. The aim of this study was to evaluate the changes in the blood levels of fatty acids and prostacyclin (PGI2) and thromboxane (TXA2) in the weanling rat caused by the dietary intake of nucleotides and orotate. Three groups of rats at weaning were fed a control diet, an orotate supplemented diet (O-50) and a nucleotide supplemented diet (N-50) during 4 weeks, respectively. Absolute values of plasma polyunsaturated fatty acids greater than 18 carbon atoms of the n-6 and n-3 series were increased in the N-50 group and decreased in O-50 with regard to the control. However, the relative fatty acid composition of plasma lipid fractions was mostly unaffected. Plasma 6-keto-PGF1 alpha showed a trend to be increased in N-50 and serum TXB2 was significantly increased in that group. Both eicosanoids were unchanged by dietary orotate intake. These results may be explained because of the increased plasma 20:4n-6 found in rats fed a supplemented nucleotide diet. Thus, nucleotides present in foods appear to modulate PUFA conversion and eicosanoids synthesis in early life.  相似文献   

14.
In vascular cells, prostacyclin (PGI2) synthase (PGI2s) has been localized in the endoplasmic reticulum of endothelial cells and in the nuclear and plasma membrane of smooth muscle cells. In human umbilical vein endothelial (HUVE) cells, we detected the enzyme in abundant cytoplasmic vesicles apparently originating from the plasma membrane and similar to those stained by gold-albumin, which interacts with a caveolar receptor. This prompted us to try a direct confocal microscopy approach aimed at colocalizing gold-albumin, caveolin-1, and PGI2 synthase. Moreover, the staining of HUVE cells with an anti-BiP7Grp78 antibody (a marker of endoplasmic reticulum) shows a perinuclear localization, sharply separated from PGI2 synthase localization. The results indicate that more than 80% of the enzyme resides in cellular sites costaining with caveolin-1 antibody and gold-albumin. This evidence was confirmed by the demonstration that PGI2 synthase and caveolin-1 coimmunoprecipitate in HUVE cell lysates and that they are associated to detergent-insoluble membrane domains in the same low-density fractions of a sucrose gradient. In addition, depletion of cellular cholesterol by mevalonate and methyl-beta-cyclodextrin leads to the shift of PGI2 synthase and caveolin-1 to higher density fractions of the gradient. Biochemical evidence about colocalization was supported by the use of a fusion protein glutathione S-transferase (GST)/caveolin-1, which retained either PGI2s purified from ram seminal vesicles or PGI2s present in HUVE cell lysates. Binding of PGI2s to caveolin "scaffolding domain" and to C-terminal region was deduced by using full-length GST--Cav-1, GST--Cav 61--101, and GST C- and N-terminal fusion proteins. A double approach based on the usage of filipin as a specific caveolae-disrupting agent and antisense oligonucleotides targeting PGI2 synthase mRNA suggests that the production of PGI2 in caveolae is likely to be connected to the regulation of angiogenesis, at least in vitro.  相似文献   

15.
The number of PG12 receptors in NCB-20 neuronal hybrid cells assayed by specific [3H]iloprost binding is substantially reduced when cells are cultured in the presence of tunicamycin, the specific inhibitor of protein N-glycosylation. The effect is reversible, dose and time dependent, and is on the number of receptors not their affinity. Tunicamycin was shown to have a selective effect on glycoprotein synthesis under these conditions with only slight effects on total protein synthesis. These results are consistent with the PG12 receptor being a glycoprotein or closely associated with such a glycoprotein whose expression is dependent on N-glycosylation.  相似文献   

16.
M J Cho  M A Allen 《Prostaglandins》1978,15(6):943-954
The rate constant for the hydrolysis of prostacyclin (PGI2) to 6-keto-PGF1alpha was measured by monitoring the UV spectral change, over a pH range 6 to 10 at 25 degrees C and the total ionic strength of 0.5 M. The first-order rate constant (kdegreesobs) extrapolated to zero buffer concentration follows an expression, kdegreesobs = kH+ (H+), where kH+ is a second-order rate constant for the specific acid catalyzed hydrolysis. The value of kH+ obtained (3.71 x 10(4) sec-1 M-1) Is estimated approximately 700-fold greater than a kH+ value expected from the hydrolysis of other vinyl ethers. Such an unusually high reactivity of PGI2 even for a vinyl ether is attributed to a possible ring strain release that would occur upon the rate controlling protonation of C5. A Br?nsted slope (alpha) of 0.71 was obtained for the acid (including H3O+) catalytic constants, from which a pH independent first-order rate constant for the spontaneous hydrolysis (catalyzed by H2O as a general acid) was estimated to be 1.3 x 10(-6) sec-1. An apparent activation energy (Ea) of 11.85 Kcal/mole was obtained for the hydrolysis at pH 7.48, from which a half-life of PGI2 at 4 degrees C was estimated to be approximately 14.5 min. when the total phosphate concentration is 0.165 M (cf. 3.5 min. at 25 degrees C).  相似文献   

17.
Prostacyclin (PGI2) produces an antiarrhythmic effect on aconitine induced arrhythmias in rats. The ED50 of PGI2 was 0.7 microgram/kg and the maximum antiarrhythmic effect 54 per cent. The equi-effective doses of PGE2 and PGF2alpha were higher (ED50 of PGF2alpha = 1.2 microgram/kg, ED50 of PGE2 = 2.7 microgram/kg). However, PGF2alpha and PGE2 had a maximum antiarrhythmic effect of 80 per cent in this model.  相似文献   

18.
J V Levy 《Prostaglandins》1978,16(1):93-97
Prostacyclin (PGI2), in a wide concentration range, produced neither contraction nor relaxation of isolated human saphenous vein. Isolated portal veins and vena cava from normal and spontaneously hypertensive rats (SHR) responded only with an increase in contractile tension when exposed to PGI2. This constrictor effect was absent in a calcium-free buffer. PGI2 failed to relax KCI contracted vena cava. The constrictor effect of PGI2 on portal vein was attenuated in a glucose-free, oxygen deficient buffer. No tachyphylaxis or tolerance to the constrictor effect of PGI2 was noted. Results emphasize that PGI2 may produce differing effects on vascular smooth muscle tension depending on species and type of blood vessel studied.  相似文献   

19.
Prostacyclin (PGI2) is a powerful inhibitor of platelet function and recent studies have indicated that it can dissociate aggregated platelets in vivo. The present investigation has evaluated the mechanism involved in the dissociation of ADP aggregated platelets by PGI2, the influence of epinephrine on the process of PGI2 mediated disaggregation, and effects of the catecholamine on the refractory state of PGI2 dispersed cells. Dissociation of ADP aggregates by PGI2 was concentration and time dependent, caused complete disappearance of sensitive platelet clumps and restored platelet discoid form. The dispersed platelets were refractory to further stimulation by ADP, thrombin, arachidonate or the calcium ionophore, A23187. Measurement of cAMP revealed no change in control levels after aggregation by ADP, but a sharp increase during and after dissociation by PGI2. Epinephrine added to ADP aggregates before or after PGI2 blocked disaggregation, or stopped dissociation if already in progress, and caused a rapid fall in the high levels of cAMP stimulated by PGI2. Agents to which PGI2 dissociated platelets were refractory, including ADP, arachidonate and A23187 caused no lowering of elevated cAMP levels. Reduction of high levels of CAMP in PGI2 dispersed platelets by epinephrine did not result in reaggregation. However, epinephrine addition to refractory platelets restored in large measure their sensitivity to aggregation by arachidonate, thrombin, ADP and A23187.  相似文献   

20.
Prostacyclin (PGI2) stimulates platelet adenylate cyclase, elevates intracellular levels of cyclic adenosine monophosphate and blocks the response to aggregating agents. It is rapidly hydrolyzed (T 1–5 min) to 6-keto prostaglandin F at acid or neutral pH.As a result, platelets incubated with PGI2 will recover spontaneously and respond to aggregating agents within 15–60 min, depending on the initial PGI2 concentration. In the present study we have evaluated the influence of temperature and pH on the stability of PGI2 and its effects on platelet function. PGI2 in Tris buffer was stabilized at several pH levels and stored at 37°C, 23°C, and 4°C. Inhibitory influence on platelet function was lost rapidly at pH 7.2–7.4, lasted several hours at pH 7.8 and was retained indefinitely at pH 8 or above. PGI2 (2.8 hM) completely inhibited the response to arachidonic acid for 15 min. at pH 7.4, for at least 1 hour at pH 7.8 and showed no reversal of inhibition after 48 hours at pH 8. However, PGI2 inhibited samples at pH 8 completely recovered their sensitivity to arachidonic acid when the pH was reduced to 7.4. These findings indicate that the biological activity of PGI2, though labile at neutral pH, is stable at pH 8 and can inhibit cAMP mediated platelet functions for at least 48 hours. Because of its pH dependence, PGI2 may be a useful agent for prolonging the sensitivity of stored platelets.  相似文献   

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