共查询到20条相似文献,搜索用时 15 毫秒
1.
B Cooper 《Life sciences》1979,25(16):1361-1367
The effect of exposing platelets to prostaglandin D2 (PGD2) on hormone binding was studied. Incubation of platelets with PGD2 for 2 hr resulted in a decrease in [3H]PGD2 binding that was dose dependent. Inhibition of binding was 14% after incubation with 10?8M PGD2, 19% after incubation with 10?7M PGD2, and 40% after exposure to 10?6M PGD2. This decreased binding (desensitization) was specific for [3H]PGD2 as binding to platelets by [3H]PGE1 and the α-adrenergic antagonist [3H] dihydroergocryptine (DHEC) was comparable to control platelets. Saturation of [3]PGD2 binding to desensitization platelets was at 27 fmole ligand/108 platelets compared to 43 fmoles/108 platelets in control platelets. Half-maximal saturation occured at 20 nM PGD2 both for desensitized and control platelets, suggesting that decreased binding sites rather than altered affinity between ligand and receptor accounted for these results. These platelets had a partial increase in [3H]PGD2 binding a few hours after plasma was washed free of PGD2 with complete resensitization after 24 hr. Since prostaglandins such as PGI2, PGD2, and PGE1 are potent inhibitors of platelet aggregation, decreased binding of platelets to these hormones after prostaglandin exposure may provide a mechanism for altered responsiveness of platelets to aggregating stimuli. 相似文献
2.
Dale L. Birkle Kathy F. Wright Cathy K. Ellis Earl F. Ellis 《Prostaglandins & other lipid mediators》1981,21(6):865-877
The levels of PGD2, PGE2, PGF2α and 6-keto-PGF1α (6KF1α) produced from endogenous archidonic acid (AA) were quantitated in cat cerebral cortical homogenates and microvessels isolated from cat cerebral cortex using gas chromatography/mass spectrometry (GC/MS). There was a six-fold enrichment of 6KF1α levels in isolated microvessels, compared to homogenates, suggesting that 6KF1α is of vascular, rather than neuronal origin. In order to further understand any possible role that norepinephrine (NE)_might have on modulation of PG synthesis, we studied the effects of 0.5 mM NE on PG synthesis from endogenous AA and from 3H-PGG2, the endoperoxide precursor of PGs. In cat cortical homogenates NE induced a 74% increase in PGD2 and PGF2α, a 62% increase in PGE2, and a 36% increase in 6KF1α, as measured by GC/MS. NE caused a twofold increase in the conversion of 3H-PGG2 to 3h-PGG2α, with a concomitant decrease in 3H-PGE2 and 3H-6KF1α formation, and no change in 3H-PGD2 synthesis. NE had no effect on the total conversiob of 3H-PGG2 to 3H-PGs, nor on the breakdown of 3H-PGG2 in the absence of brain tissue. We conclude that NE stimulates extravascular synthesis of PGD2, PGE2 and PGF2α by stimulation of the prostaglandin synthetase complex, in addition to NE's stimulatory effect on the conversion of PGG2 to PGF2α, and that the lack of effect of NE on 6KF1α synthesis reflects either a failure to achieve an adequate concentration at the vascular tissue, or an absence of the mechanism whereby NE stimulates PG synthetase. 相似文献
3.
The activity of prostacyclin (PGI2), PGE1 or PGD2 as inhibitors of platelet aggregation in plasma from human, dog, rabbit, rat, sheep and horse was investigated. Prostacyclin was the most potent inhibitor in all species. PGD2 was a weak inhibitor in dog, rabbit and rat plasma whereas PGE1 and prostacyclin were highly active. Theophylline or dipyridamole potentiated the inhibition of human platelet aggregation by prostacyclin, PGE1 or PGD2. Compound N-0164 abolished the inhibition by PGD2 of human platelet aggregation but did not inhibit the effects of PGE1 or prostacyclin. The results suggest that prostacyclin and PGE1 act on similar sites on platelets which are distinct from those for PGD2. 相似文献
4.
Barry Cooper Andrew I. Schafer David Puchalsky Robert I. Handin 《Prostaglandins & other lipid mediators》1979,17(4):561-571
Prostaglandin D2 (PGD2) is one of several prostaglandins that can inhibit platelet aggregation and activate adenylate cyclase. Platelets were exposed to varying concentrations of PGD2, washed, and the adenylate cyclase response to prostaglandins, epinephrine, and sodium fluoride determined. Incubating platelets with 5 × 10?5 M PGD2 for 2 hr resulted in a 45% decrease in PGD2 activation of adenylate cyclase and a 25% decrease in stimulation by PGE1. Fluoride activation (7-fold) epinephrine inhibition (30%) and basal enzyme activity were unchanged by exposure of the platelets to PGD2. Desensitization was concentration dependent, with loss of enzyme activity first noted when platelets were incubated with 10?7 M PGD2. Enzyme sensitivity could be partially restored when desensitized platelets were washed free of PGD2 and incubated in buffer for 2 hr; complete resensitization required incubation for 24 hr in plasma. Regulation of prostaglandin sensitive platelet adenylate cyclase could be of importance in mediating the response of platelets to aggregating agents. 相似文献
5.
M. Hamon J. Berthaut A. Wisner F. Dray B. Descomps H.Thaler Dao 《Prostaglandins & other lipid mediators》1993,46(3)
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 PGF2α > 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
6.
Ryo Kawata Yoshihiro Urade Masayoshi Tachibana Osamu Mizukoshi 《Prostaglandins & other lipid mediators》1988,35(2)
The exogenous and endogenous syntheses of prostaglandins (PG's) by the cochlea of adult mongolian gerbils were studied
. After incubation of the whole membraneous cochlea with [3H]-arachidonic acid (AA), syntheses of PGF2α, 6-keto PGF1α, PGE2, thromboxane (TX) B2 and PGD2 were evidenced in this order. The synthesis of radioactive PG's was almost completely inhibited by incubation with 10−5 M indomethacin. No significant amounts of those PG's were detected by radioimmunoassay (RIA) in the cochlea obtained from animals killed by microwave irradiation at 5.0 kw for 0.8 sec. However, when the homogenate of the whole membraneous cochlea obtained from animals without microwave irradiation was incubated at 37°C for 0–15 min, PGD2, PGE2, PGF2α and 6-keto PGF1α were found to be formed from endogenous AA in the cochlea by RIA. PG's were formed already at 0 time to considerable level (PGD2, PGF2α and 6-keto PGF1α, 90–120 pg/cochlea; PGE2, 370 pg/cochlea), reached to the maximum level (PGD2, PGF2α and 6-keto PGF1α, 170–200 pg/cochlea; PGE2, 500 pg/cochlea) at a 5-min incubation, and then gradually decreased. On the other hand, the amount of TXB2 was lower than the detection limit by RIA (<50 pg/cochlea) even after the incubation. The cochlea was dissected into three parts: organ of Corti + modiolus (OC + M), lateral wall (LW), and cochlear nerve (CN), and then PG's formed by these tissues were determined after a 5-min incubation of the homogenates. In the CN and OC + M, PGE2 was the major PG (100 and 160 pg/tissue, respectively), and the amounts of PGD2, PGF2α and 6-keto PGF1α were about
of those of PGE2. In the LW, the amounts of PGD2, PGE2, PGF2α and 6-keto PGF1α were about the same level (70–100 pg/LW). 相似文献
7.
Prostaglandin D2 was found to be a potent inhibitor of platelet aggregation. Aggregation of human platelets by ADP, collagen and prostaglandin G2 was inhibited more strongly by PGD2 than by PGE1. Although ADP-induced aggregation of rabbit platelets was inhibited more strongly by PGE1 than by PGD2 the latter prostaglandin gave a more long-lasting inhibitory effect on platelet aggregation following intravenous or oral administration. These results coupled with the finding that PGD2 has less hypotensive effects on the cardiovascular system than PGE1 suggest the possible use of PGD2 as an antithrombotic agent. 相似文献
8.
Edward E. Nishizawa William L. Miller Robert R. Gorman Gordon L. Bundy Jan Svensson Mats Hamberg 《Prostaglandins & other lipid mediators》1975,9(1)
Prostaglandin D2 was found to be a potent inhibitor of platelet aggregation. Aggregation of human platelets by ADP, collagen and prostaglandin G2 was inhibited more strongly by PGD2 than by PGE1. Although ADP-induced aggregation of rabbit platelets was inhibited more strongly by PGE1 than by PGD2 the latter prostaglandin gave a more long-lasting inhibitory effect on platelet aggregation following intravenous or oral administration. These results coupled with the finding that PGD2 has less hypotensive effects on the cardiovascular system than PGE1 suggest the possible use of PGD2 as an antithrombotic agent. 相似文献
9.
10.
Noboru Toda 《Prostaglandins & other lipid mediators》1982,23(1):99-112
The addition of prostaglandin (PG) D2 contracted helical strips of dog cerebral, coronary, renal and femoral arteries; the contraction was greatest in cerebral arteries. The contractile response of cerebral arteries was potentiated by aspirin and attenuated by polyphloretin phosphate. In the arterial strips contracted with PGF2α, PGD2 elicited a concetration-related relaxation; the relaxation was greatest in mesenteric arteries. In mesenteric arterial strips contracted with norepinephrine, a lesser degree of relaxation was induced, and in the K+-contracted arteries, only a contraction was induced. Treatment with PGD2 attenuated the contractile responses of cerebral and mesentric arteries to PGF2α or PGE2; this inhibitory effect was approximately 10 times greater in mesenteric arteries. However, the response to serotonin (for cerebral arteries) or norepinephrine (for mesenteric) was unaffected. It may be concluded that the heterogeneity of response to PGD2 of a variety of dog arteries is due to different contributions of vasoconstrictor and vasodilator mechanisms. PGD2 appears top share the mechanism underlying arterial contraction with PGF2α and PGE2, and interferes with the effect of these PG's possibly on receptor sites. 相似文献
11.
Shizuko Takano Shigeru Itagaki Kunio Sakurai Takehiko Suzuki 《Prostaglandins & other lipid mediators》1980,20(3):579-586
Influences of prostaglandin(PG)s on electrophoretic mobilities and aggregation of rabbit platelets were studied. The PGs studied (PGI2, PGE1, PGD2, PGE2, PGF2α, PGA2 and PGA1) had no effect on platelet electrophoretic mobility. However, both PGE1 and PGI2 in 0.3 and 3.0 μM inhibited ADP-induced aggregation and ADP-induced decrease in the mobility. PGD2 in 0.3 and 3.0, and PGE2 in 30 μM inhibited the aggregation but did not depress the ADP-induced decrease in the mobility. PGF2α, PGA2 and PGA1 had no effect on the decrease in electrophoretic mobility and on the aggregation caused by ADP. 相似文献
12.
Prostacyclin (PGX) strikingly increases cyclic AMP concentrations in human platelets. Prostacyclin is approximately 10 times more active than PGD2, 30 times more active than PGE1 and more than 1000 times more active than its stable end product, 6-oxo-PGF1α.These results correlate well with the anti-aggregating activity of prostacyclin, compared with PGE1 and PGD2. 相似文献
13.
M. Lombroso S. Nicosia R. Paoletti B.J.R. Whittle S. Moncada J.R. Vane 《Prostaglandins & other lipid mediators》1984,27(2):321-333
Prostacyclin, (PGI2) is a potent but unstable inhibitor of platelet aggregation, probably acting through stimulation of adenylate cyclase.A stable analogue of prostacyclin with antiaggregatory properties, 5,6-dihydro-PGI2 (6β-PGI), and PGE1 can compete for the binding sites labelled by 3H-PGI2 in human platelet membranes (the affinity being PGI2 > PGE1 > 6β -PGI1). Both 6β-PGI1 and PGE1, as well as PGI2, bind to two classes of binding sites. 6β -PGI1 and PGE1 activate adenylate cyclase to the same extent as PGI2,with a rank order of potency which parallels that observed in binding experiments. The stimulation of this enzyme is brought about by interaction of each these prostanoids with two different classes of components. The comparison of binding and adenylate cyclase data suggests that the sites to which PGI2, 6β -PGI1 and PGE1 bind might be coupled to the activation of adenylate cyclase. Since 6β-PGI1 seems to act through the same molecular mechanisms as PGI2, because of its stability it is an useful tool to investigate the mode of action of prostacyclin in platelets. 相似文献
14.
A charcoal adsorption method was developed to measure specific prostaglandin binding in low speed supernates of hamster myometrial homogenates. This method was used to characterize and quantitate PGE1-specific binding. The equilibrium binding constants and the concentration of specific PGE1 binding sites were determined during the hamster estrous cycle. The apparent association constant for 12 different preparations was 1.16 ± 0.08 × 109M−1. The concentration of PGE1 specific binding sites was significantly higher on Days 2 and 3 of the estrous cycle than it was on Days 1 or 4. The competition for PGE1 binding sites by PGE2, PGF2α, PGA1 and various PGE1 metabolites and derivatives was measured in hamster myometrial homogenates. Relative affinities of the natural prostaglandins for the PGE1 binding sites, calculated by parallel line assay, were: PGE2>PGE1>PGA1>PGF2α. For PGE1 metabolites the relative affinities were: PGE1>13,14-dihydro-PGE1>13,14-dihydro-15-keto-PGE1>15-keto-PGE1. For the analogs and derivatives the compounds tested ranked as: 16,16-dimethyl-PGE1≥PGE1>PGE1 methyl ester>17-phenyl-18,19,20-trinor-PGE1>15(S)15-methyl-PGE1 methyl ester. Arachidonic acid, bis-homo-γ-linolenic acid and 7-oxa-13 prostynoic acid had relative affinities ≥0.1 compared to PGE1=100. Indomethacin had a relative affinity of 0.4 compared to PGE1. 相似文献
15.
Frances A. Kimball Kenneth T. Kirton Lillian J. Wyngarden 《Prostaglandins & other lipid mediators》1975,10(5):853-864
Myometrial low speed supernatant prepared from non-pregnant rhesus uteri was incubated with 3H-Prostaglandin (PG)E1 with or without addition of unlabelled prostaglandins. The uptake of 3H-PGE1 was inhibited in a dose dependent fashion by PGE2>PGE1>PGA1>PGF2α=PGA1>PGB1=PGB2≥PGD2. PGE1 metabolites inhibited 3H-PGE1 binding in the following order: 13,14-dihydro-PGE1>13,14-dihydro-15-keto-PGE1=15-keto-PGE1. The specific binding of 3H-PGE1 and 3H-PGF2α was similarly affected by the temperature and time of incubation. Equilibrium binding constants determined using rhesus uteri obtained during the luteal phase of the menstrual cycle indicate the presence of high affinity PGE1 binding sites with an average (n=3) apparent dissociation constant of 2.2 × 10−9M and a lower affinity PGE1 binding site with a Kd ≅ 1 × 10−8M. No high affinity — low capacity 3H-PGF2α sites could be demonstrated.Relative uterine stimulating potencies of some natural prostaglandins and prostaglandin analogs tested after acute intravenous administration in mid-pregnant rhesus monkeys corresponded with the PGE1 binding inhibition of the respective compound. The uterine stimulating potencies of the prostaglandin analogs tested were: (15S)-15-methyl-PGE2=16,16-dimethyl-PGE2>17-phenyl-18,19,20-trinor-PGE2>16 phenoxy-17,18,19,20-tetranor-PGF2α=PGE2=PGE1=(15S)-15-methyl-PGF2α>PGF2α. 相似文献
16.
The response of endothelial adenylate cyclase (AC) to prostaglandins (PGE1, PGE2, PGF1α, PGF2α, PGD2 and PGI2) and the relationship of PGE2 to adrenergic systems were investigated in cerebrovascular endothelial cultures. E-type prostaglandins and PGI2 were more effective in stimulating endothelial AC (EC50 = 3 × 10?7M, and 3 × 10?7M, respectively) than prostaglandins of the F-series and PGD2 which activated AC at high doses only. A modulation of endothelial AC response to either PGE2 or norepinephrine (NE) was observed in the presence of both agents in the system. It was manifested by a dose-dependent NE inhibition of the PGE2-stimulated formation of cAMP, which was partially restored by phentolamine. Alpha and β-adrenergic agonists (α, clonidine and 6-fluoronorepinephrine; β, isoproterenol) also partly blocked while forskolin and PGE2 synergistically stimulated the production of cAMP in the endothelial cultures. These findings strongly suggest that the interaction of prostaglandins and α- and β-adrenergic agonists with the AC system in cerebrovascular endothelium may play a role in the regulation of the cerebral microcirculation and/or blood pressure. 相似文献
17.
Philip Needleman Mark O. Whitaker Angela Wyche Karin Watters Howard Sprecher Amiram Raz 《Prostaglandins & other lipid mediators》1980,19(1):165-181
Addition of the one-, two- or three- series endoperoxide to human platelet-rich plasma tend to supress aggregation, through the action of their respective non-enzymatic breakdown products PGE1, PGD2, or PGD3 all of which elevate cyclic AMP levels. On the other hand, these stable primary products do not arise in appreciable amounts from intrinsic endoperoxides generated from either endogenous or exogenous free fatty acids. 5,8,11,14,17-Eicosapentaenoic acid (EPA) suppresses arachidonic acid (5,8,11,14-eicosatetraenoic acid) conversion by cycloogygenase (as well as lipoxygenase) to aggregatory metabolites in platelets. Exogenously added EPA was capable of inhibiting PRP aggregation induced either by exogenous or endogenous (released by ADP or collagen) arachidonate. The hypothetical combination of an EPA-rich diet and a thromboxane synthetase inhibitor might abolish production of the pro-aggregatory species, thromboxane A2, and enhance formation of the anti-aggregatory metabolite, prostacyclin.Whereas EPA is not detectably metabolized by platelets, dihomo-γ-linolenic acid (8,11,14,-eicosatrienoic acid) is primariley converted by cyclooxygenase and thromboxane synthetase into the inactive metabolite, 12-hydroxyheptadecadienoic (HHD) acid. Pretreatment of human platelet suspensions with the thromboxane synthetase inhibitor imidazole unmasks the aggregatory property of PGH1 and DLL which was partially compromised by the PGE1 formed. The combination of the thromboxane synthetase inhibitor and an adenylate cyclase inhibitor unmasks a complete irreversible aggregation by DLL or PGH1. The basis of a dietary strategy that replaces AA with DLL must rely on the production by the platelet of an inactive metabolite (HHD) rather than thromboxane A2. 相似文献
18.
Ph.D. David I. Wilkinson Ph.D. Elaine K. Orenberg 《Prostaglandins & other lipid mediators》1979,17(3):419-429
Guinea pig ear epidermal cells (keratinocytes) were established in primary cultures using trypsin, and treated in their proliferative phase of growth with prostaglandins E1, D1, F1α, E2, D2, or F2α. This phase is induced by the addition of retinoic acid during cell plating. Intracellular content of cAMP and cGMP was measured by radioimmunoassay at various times after treatment.Maximum stimulation of cAMP levels was observed with PGD2, smaller increases with PGE2 and relatively transient rises with PGF2α which were of low significance, but confirm earlier data. Similar results were observed with PGD1, PGE1, and PGF1α with smaller increases. The effects of D and E PGs were biphasic. Significant increases in cGMP were immediately observed with PGD2 and PGE2. With PGF2α, maximum cGMP levels were noted after some delay.All PGs tested showed some effect in elevating cyclic nucleotides in keratinocytes. The most striking result was the increase in cAMP on PGD2 treatment. 相似文献
19.
T V Zenser C A Herman R R Gorman B B Davis 《Biochemical and biophysical research communications》1977,79(2):357-363
Kidney membrane fractions metabolized [1-14C]PGH2 to TXB2, PGE2, PGF2α, PGD2, 6-keto PGF1α, and HHT. TXA2, as measured by TXB2, was enzymatically formed in cortex microsomes and was identified by thin layer chromatography and gas chromatography - mass spectrometry. PGH2 caused a labile inhibition of cortical PGE2-stimulated adenylate cyclase. PGE2, PGF2α, and PGD2 are stimulators of cortical adenylate cyclase. The inability of two thromboxane synthetase inhibitors, imidazole and 9,11-azoprosta-5,13 dienoic acid, to block PGH2 inhibition suggested that TXA2 was not an obligatory intermediate in this process. Therefore, a potential function of cortical PGH2 is inhibition of adenylate cyclase. 相似文献
20.
A method for the preparation of a highly purified sample of rabbit blood monocytes is described. The metabolism of arachidonic acid (AA) in these cells was studied. Mononuclear cells were prepared by centrifugation on Ficoll-Paque gradients and the monocytes were obtained by further centrifugation and adherence onto plastic culture dishes. These procedures provided a preparation which contained 95% monocytes (non-specific esterase positive). Incubation of [1-14C]-AA with these cells produced four major metabolites which were separated by TLC; these corresponded to prostaglandin (PG) D2, thromboxane (TX) B2, 12-hydroxyheptadecatrienoic acid (HHT) and 12-/15- hydroxyeicosatetraenoic acid (HETE). A minor product which co-migrated with PGE2 was also detected but neither 6-keto-PGF1α nor PGF2α were detected. Also, there was no evidence of the formation of 5-lipoxygenase products (5-HETE and LTB4) by rabbit monocytes with or without calcium-ionophore A23187-stimulation. The production of PGD2, TXB2 and PGE2 was further confirmed by analyzing [3H]-AA metabolites using high-performance liquid chromatography (HPLC) with tritiated standards as references. The biosynthesis of these compounds from endogenous substrate in A23187-stimulated monocytes was confirmed by specific radioimmunoassays with or without prior HPLC separation. The synthesis of immunoreactive LTB4 and LTC4 by A23187-stimulated cells was also monitored and found to be relatively low. The synthesis of PGD2, TXB2 and PGE2 from both exogenous and endogenous substrate was suppressed by treatment of the monocytes with indomethacin (10−6 M). 相似文献