共查询到20条相似文献,搜索用时 15 毫秒
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Johannes D. Veldhuis Patricia Klase Laurence M. Demers 《Prostaglandins & other lipid mediators》1982,23(3)
Granulosa cells isolated from mature Graafian follicles of swine produced significant quantities of immunoreactive 6-keto-PGF1α under chemically defined conditions in vitro. Luteinizing hormone elicited a dose-dependent stimulation of 6-keto-PGF1α accumulation, but follicle stimulating hormone, prolactin, L-epinephrine, estradiol-17B, or PGE2 were devoid of effect. The time-dependent in vitro production of 6-keto-PGF1α by ovarian cells was susceptible to inhibition by indomethacin, U-51506, cycloheximide, and actinomycin D. These observations implicate granulosa cells in the specific and hormonally regulated production of prostacyclin. 相似文献
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Physiologic concentrations of insulin completely inhibited the norepinephrine-induced increment in the production of 6-keto-prostaglandin (PG) F1α, the stable derivative of prostacyclin (PGI2), by isolated rat adipocytes. The inhibition of PGI2 production by insulin in isolated rat adipocytes supports the view that the elevated plasma level of 6-keto-PGF1α in rats with non-ketotic diabetes mellitus and diabetic ketoacidosis is derived at least in part from production of PGI2 by the adipocyte cell mass. 相似文献
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In order to investigate the mechanism behind ventilation-induced pulmonary prostacyclin production at birth, chloralose anesthetized, exteriorized, fetal lambs were ventilated with a gas mixture that did not change blood gases (fetal gas) and unventilated fetal lungs were perfused with blood containing increased O2 and decreased CO2. Ventilation with fetal gas (3%O2, 5%CO2) increased net pulmonary prostacyclin (as 6-keto-PGF1 alpha) production from -5.1 +/- 4.4 to +12.6 +/- 7.6 ng/kg X min. When ventilation was stopped, net pulmonary prostacyclin production returned to nondetectable levels. Ventilation with gas mixtures which increased pulmonary venous PO2 and decreased PCO2 also stimulated pulmonary prostacyclin production, but did not have greater effects than did ventilation with fetal gas. In order to determine if increasing PO2 or decreasing PCO2 could stimulate pulmonary prostacyclin production independently from ventilation, unventilated fetal lamb lungs were perfused with blood that had PO2 and PCO2 similar to fetal blood, blood with elevated O2, and blood that had PO2 and PCO2 values similar to arterial blood of newborn animals. Neither increased O2 nor decreased CO2 in the blood perfusing the lungs stimulated pulmonary prostacyclin synthesis. We conclude that the mechanism responsible for the stimulation of pulmonary prostacyclin production with the onset of ventilation at birth is tissue stress during establishment of gaseous ventilation and rhythmic ventilation. 相似文献
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Ralph T Schermuly Soni S Pullamsetti Susanne C Breitenbach Norbert Weissmann Hossein A Ghofrani Friedrich Grimminger Sigrid M Nilius Karsten Schrör Jutta Meger-Kirchrath Werner Seeger Frank Rose 《Respiratory research》2007,8(1):4-13
Background
The rapid desensitization of the human prostacyclin (IP) in response to agonist binding has been shown in cell culture. Phosphorylation of the IP receptor by protein kinase C (PKC) has been suggested to be involved in this process.Methods and results
In this study we investigated the vasodilatory effects of iloprost, a stable prostacyclin analogue, in perfused rabbit lungs. Continuous infusion of the thromboxane mimetic U46619 was employed to establish stable pulmonary hypertension. A complete loss of the vasodilatory response to iloprost was observed in experiments with continuous iloprost perfusion, maintaining the intravascular concentration of this prostanoid over a 180 min period. When lungs under chronic iloprost infusion were acutely challenged with inhaled iloprost, a corresponding complete loss of vasoreactivity was observed. This desensitization was not dependent on upregulation of cAMP-specific phosphodiesterases or changes in adenylate cyclase activity, as suggested by unaltered dose-response curves to agents directly affecting these enzymes. Application of a prostaglandin E1 receptor antagonist 6-isopropoxy-9-oxoxanthene-2-carboxylic acid (AH 6809) or the PKC inhibitor bisindolylmaleimide I (BIM) enhanced the vasodilatory response to infused iloprost and partially prevented tachyphylaxis.Conclusion
A three-hour infusion of iloprost in pulmonary hypertensive rabbit lungs results in complete loss of the lung vasodilatory response to this prostanoid. This rapid desensitization is apparently not linked to changes in adenylate cyclase and phosphodiesterase activation, but may involve PKC function and co-stimulation of the EP1 receptor in addition to the IP receptor by this prostacyclin analogue. 相似文献6.
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F.A.M. Peeters R. Van Den Bossche H. Bult A.G. Herman 《Prostaglandins, leukotrienes, and essential fatty acids》1991,43(4):239-246
We investigated whether prostacyclin formation by the isolated rabbit lung can serve as a measure of pulmonary distress. The basal TXA2 and PGI2 formation was very low, and depended on the preperfusion history of the lung (low or high flow, use of dextran or artificial perfusate). The basal prostanoid production remained unchanged over a time period of 2 h. Neither was it influenced by the serotonin uptake inhibitor chlorimipramine and by small changes in temperature (33 degrees C vs 39 degrees C). The PGI2 formation was almost independent of hemodynamic alterations such as embolism or vasoconstriction. An enhanced production was only seen after a dramatic increase in flow (from 1.7-5 ml/sec), and a transient 3-fold increase was observed after administration of 1 mM H2O2. A substantial (up to 40-fold) but transient increase in TXA2 production was measured after 1 mM of H2O2, and the TXA2 production was positively correlated to the increase in pulmonary arterial pressure. However, thromboxane production was also dramatically augmented by hemodynamic alterations such as embolism, increased flow and--to a lesser extent--vasoconstriction. We conclude that the determination of the prostanoid production (and particularly the TXA2 formation) by the rabbit lung cannot be used as a direct measure of endothelial distress. To this end it is excessively biased by hemodynamic alterations such as recruitment and shear stress. 相似文献
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M L Ellsworth T J Gregory J C Newell 《Journal of applied physiology (Bethesda, Md. : 1985)》1983,55(4):1225-1231
We evaluated the effects of an abrupt increase in flow and of a subsequent sympathetic nerve stimulation on the pulmonary production of prostacyclin (PGI2) and thromboxane A2 (TXA2) in canine isolated left lower lobes perfused in situ with pulsatile flow. When flow was abruptly increased from 50 +/- 3 to 288 +/- 2 ml/min, mean pulmonary arterial pressure (Ppa) increased by 15 +/- 2 Torr and then declined by 2.4 Torr over the next 5 min. This secondary decrease in Ppa was associated with a significant 0.26 +/- 0.11 ng/ml increase in the pulmonary venous concentration of the stable PGI2 hydrolysis product 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) as determined by radioimmunoassay. Stimulation of the left stellate ganglion usually resulted in an increase in Ppa which peaked at 1.1 +/- 0.6 Torr above its prestimulus level and then declined over the next 5 min. Associated with this decline was a 0.24 +/- 0.11 ng/ml increase in 6-keto-PGF1 alpha at 1 min. We suggest that the decline in Ppa is due to the synthesis and release of PGI2 by the endothelial cells in response to an increase in perfusion pressure. 相似文献
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E V Younglai 《Journal of reproduction and fertility》1975,45(3):575-582
Graafian follicles from New Zealand white rabbits were incubated at 37 degrees C for various periods of time with air as the gas phase. Media were changed every 15 min and stored at -15 degrees C until analysed for progestins, 17 beta-hydroxyandrogens and oestrogens using established radioimmunoassay procedures. At fixed times after the start of the incubations, media containing various test substances were added with subsequent replacement by medium alone. Addition of 5 mug LH/ml for 1 sec caused a dramatic increase in the synthesis and secretion of androgen with lesser increases in progestin and oestrogen. Puromycin and cycloheximide but not actinomycin D, inhibited LH-induced steroidogenesis. Cycli AMP, dibutyryl cycli AMP, cyclic CMP, 5'-AMP, and theophylline also caused an increase in androgen production which rapidly ceased when media without nucleotides were added. Sodium fluoride had no effect on steroidogenesis. From these data it was concluded that (i) the rabbit follicle is the major source of ovarian androgen; (ii) the binding of LH to the follicular cells is a rapid process; (iii) the events following LH binding do not require the presence of LH in the medium; (iv) cyclic nucleotides which may act as second messengers also stimulate steroidogenesis; (v) the effects of LH and cyclic nucleotides on steroidogenesis are different; and (vi) the action of LH on follicular steroidogenesis probably occurs in the translational level. 相似文献
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Adenosine production by isolated rat heart mitochondria was examined and was observed to be dependent on an active adenine nucleotide transporter and a functional 5'-nucleotidase. It was found that mitochondria do not transport adenosine. These results suggest that mitochondria provide AMP for an extramitochondrial 5'-nucleotidase and this was verified by direct measurement of extramitochondrial levels of AMP and adenosine. A possible role for mitochondria in myocardial adenosine production is discussed. 相似文献
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Triphasic response of prostacyclin production in rabbit thoracic aorta in early atherosclerosis 总被引:1,自引:0,他引:1
S I Myers D H Russell L Parks M K Reed 《Prostaglandins, leukotrienes, and essential fatty acids》1991,44(1):31-36
Atherosclerosis was induced in male rabbits by administration of a 2% cholesterol diet for up to 18 weeks. The animals were assessed for aortic microsomal prostanoid synthesis, morphologic assessment and serum cholesterol levels. Serum levels of cholesterol increased from control values of 84 +/- 9 ng/dl to 1632 +/- 227 ng/dl at 2 weeks (20-fold increase), and 4859 +/- 829 ng/dl at 9 weeks (57-fold increase). Aortic microsomal prostacyclin synthesis fell significantly at 2 weeks of cholesterol feeding which predated the morphologic appearance of atherosclerotic plaque in the 7 week group. Aortic microsomal PGI2 synthesis significantly increased by 7 weeks and did not fall until the 18 week group when a highly significant increase in aortic plaque developed. These findings suggest a triphasic response of aortic PGI2 synthesis with the development of early atherosclerosis. Phase one is a fall in aortic PGI2 synthesis which predates the appearance of plaque. In phase 2, a significant rise in aortic PGI2 with the appearance of plaque could represent compensation of aortic endothelium to prevent further plaque development. In phase 3, decreased aortic PGI2 could indicate replacement of normal endothelium by atherosclerotic plaque. 相似文献
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Dissociation of beta-adrenergic stimulation of renin secretion and prostacyclin synthesis in the rabbit kidney 总被引:1,自引:0,他引:1
The effect of inhibition of prostaglandin (PG) synthesis with indomethacin on basal and isoproterenol-stimulated renin secretion was examined in the isolated perfused rabbit kidney. 6-keto PGF1 alpha' the stable metabolite of prostacyclin, was measured in urine by radioimmunoassay using 125I labelled histamine coupled to 6-keto PGF1 alpha as ligand. The level in urine, prior to isolation and perfusion of the kidney, was 10.7 +/- 5.6 ng/min, and this was reduced to 0.32 +/- 0.25 ng/min (P less than 0.05) in rabbits treated with 2.0 mg/kg of indomethacin. Renin release was markedly stimulated by intrarenal infusion of isoproterenol (0.1 microgram/min) but urinary 6-keto PGF1 alpha did not change. These responses were not affected by indomethacin treatment. Renal perfusion pressure, perfusate flow rate and consequently renal vascular resistance, remained relatively constant during the course of perfusion and were unaltered by indomethacin treatment. These results therefore do not support a role for PGs, and in particular prostacyclin, in the renin response to beta-adrenergic stimulation with isoproterenol. 相似文献
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Male rabbits were exposed to a single irradiation dose of 1000-5000 rad when 12, 15, 16, and 17 months old and were killed when 18 months old (i.e., 1, 2, 3, and 6 months after irradiation). Even after this long interval after irradiation, abdominal aortic prostacyclin formation was significantly depressed, whereas the nonirradiated thoracic aortic segment exhibited no significant alteration in vascular PGI2 generation. The data show that the severe decrease in PGI2 synthesis was not caused by deendothelialization induced by irradiation alone. The data support the view that a deterioration in the prostaglandin system regulating hemostatic balance is an important determinant in the development of radiation-induced vasculopathy. 相似文献
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Properties of membrane ion conductances evoked by hormonal stimulation of guinea-pig and rabbit isolated hepatocytes 总被引:2,自引:0,他引:2
T Capiod D C Ogden 《Proceedings of the Royal Society of London. Series B, Containing papers of a Biological character. Royal Society (Great Britain)》1989,236(1283):187-201
Membrane conductance changes evoked in isolated guinea-pig or rabbit hepatocytes by hormonal stimulation were studied with the whole-cell patch clamp technique. In Cl-containing solutions, noradrenaline (NA), ATP or angiotensin II (AII) evoked an increase of conductance to both K (GK) and Cl (GCl) ions. Activation of GK occurred after a delay of several seconds and was sustained in the presence of hormone. Activation of GCl was transient, lasting several seconds, and arose either at the same time or shortly after the increase in GK. Conductances showed an initial rapid rise and slow oscillatory changes during maintained hormone application. The NA-induced current reversed at -19 mV in Cl solutions, between the equilibrium potentials for chloride (ECl = 0 mV) and potassium ions (EK = -85 mV), and at -75 mV, near EK, in Cl-free solution. In both conditions whole-cell current-voltage curves were linear in the range -100 mV to +40 mV. The conductance increase produced by NA to Cl- ions was about 50 nS, that to K+ ions was 6 nS. The potassium conductance increase was abolished by the polypeptide toxin apamin (50 nM). An increase in membrane current noise was associated with NA-evoked outward K+ current and blocked by apamin. Spectral analysis gave estimates of the elementary K channel conductance of 1.7 pS. Power spectra were fitted by two Lorentzian components, with average half-power frequencies of 2 and 190 Hz. These results are discussed in relation to the single-channel properties and indicate that the open probability of K channels during the NA response is high. In Cl solutions, with apamin to block the K conductance, no increase in current noise was detected during the large Cl conductance evoked by NA. This suggests either that Cl channels are of very low unitary conductance (less than 1 pS) or that Cl transport is due to a membrane carrier. The complex time-course of hormonally evoked conductances is not due to the properties of ion conductances per se but probably to underlying changes of intracellular second-messenger concentration. 相似文献
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In vitro PGI2 synthesis by aortic strips obtained from thoracic aorta of rabbits fed a high cholesterol diet was examined and compared with that of control rabbits fed a normal diet. In this report, the amounts of PGI2 produced were shown as 6-keto-PGF1 alpha per microgram of aortic tissue DNA instead of per mg wet weight. We also investigated PGI2 synthesis by cultured smooth muscle cells (SMC) obtained from atherosclerotic intima. Basal PGI2 production by aortic strips from atherosclerotic rabbit aorta was significantly augmented compared with that of controls. Arachidonic acid (AA)-induced PGI2 production by atherosclerotic aorta was also significantly higher than that of controls. PGI2 producing capacities of intimal and medial layers, separated from atherosclerotic aorta, were examined and the intimal layer was found to elicit a significantly greater PGI2 production than the medial layer. Furthermore, cultured intimal SMC obtained from atherosclerotic rabbit aorta produced a greater amount of PGI2 than medial SMC from normal rabbit aorta at various cultured conditions. These results suggest that the possibility of enhanced PGI2 production by atherosclerotic aorta may well be considered as a defence mechanism of the vessel wall against damaging stimuli. 相似文献
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The production of prostacyclin by rings of rabbit aorta was assessed by the radioimmunoassay of 6-K-PGF1α. In steady-state conditions, the rings released 11 ng 6-K-PGF1α per 100 mg tissue in 30 min. Acetylcholine increased this output: a significant effect was detected at 1 μM and at 10 μM the amplitude of stimulation was 10-fold. The production of PGE2 and PGF2α was also increased, but to a lesser extent. The stimulatory action of acetylcholine was mimicked by carbamylcholine and inhibited by atropine; it was abolished in a calcium-free medium. Dog and rat aorta also produced more 6-K-PGF1α in response to cholinergic agonists. A short rubbing of the intimal surface of the aorta removed the layer of endothelial cells and completely abolished the cholinergic effect. It is concluded that in the aorta, cholinergic agonists, acting on a muscarinic receptor, stimulate the production of prostacyclin by endothelial cells. 相似文献
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D K Miller S Sadowski D D Soderman F A Kuehl 《The Journal of biological chemistry》1985,260(2):1006-1014
A bovine aortic endothelial cell (EC) line released prostacyclin (greater than 1 pmol/10(+5) EC cells) when incubated with fMet-Leu-Phe (FMLP)-stimulated rat and human neutrophils (PMNs). This prostaglandin (PG) I2 was shown to come from the ECs and not from the PMNs by radioactive, high-performance liquid chromatography, and immunochemical criteria. Both FMLP-stimulated rat peritoneal and human peripheral PMNs as well as their stimulated cell-free supernatants and unstimulated sonicates could elicit the release of PGI2 from ECs. Since phorbol myristate acetate stimulated PMN adherence but elicited little PGI2 release from ECs, the PGI2 stimulation in ECs is unrelated to PMN adhesion. The addition of catalase and superoxide dismutase to FMLP-stimulated PMNs enhanced rather than reduced PGI2 formation, indicating that activated oxygen products of the PMN are not responsible for the induction of PGI2. Incubation of ECs with leukotriene (LT) B4, LTC4, or LTD4 did not trigger PGI2 release nor did aspirin pretreatment of the PMNs reduce the PGI2 induction. These data suggest that arachidonic acid metabolites of the PMNs were not responsible for the PGI2 induction. Available data indicates that the PMN factor that stimulates PGI2 from ECs is either released concomitantly with the azurophilic granules or is closely related to this event. 相似文献
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K. Rajkumar L.W. Coons M.J.K. Harper A. Johns 《Prostaglandins & other lipid mediators》1981,21(6):889-897
The effect of longitudinal and circular stretch on the amounts of Prostaglandin F (PGF) and Prostaglandin E (PGE) found in the fluid bathing rabbit oviductal isthmus has been investigated. It was found that the amounts of PGE nad PGF measured in the bathing fluid of longitudinally or circularly stretched tissues were negatively correlated to the maturity of the animal. Prostaglandin E increased with time in the tissues under longitudinal and circular tension. Prostaglandin F also increased with time under longitudinal tension but remained fairly constant under circular tension. Increasing the load from 0.5 to 2.0 g had no significant effect on PGE found under longitudinal or circular tension or on PGF found under longitudinal tension. Under circular tension, PGF found increased. Transmural stimulation at 20 Hz increased PGE 8-fold over control values while PGF increased only 1 to 3-fold. It is suggested that distension of the rabbit oviductal isthmus results in increased PGF production, which could be important in ovum transport. 相似文献