共查询到20条相似文献,搜索用时 31 毫秒
1.
A. Morita H. Nishino M. Mori K. Hasegawa K. Sakai S. Kobayashi 《Prostaglandins & other lipid mediators》1979,18(4):529-540
The influences of epoxymethano and epoxycarbonyl analogs of PGH1 on washed rabbit platelets, isolated smooth muscles and perfused heart preparations were investigated. On washed rabbit platelets, 11,9-epoxy-methano and 11,9-epoxycarbonyl PGH1 produced a platelet aggregation whereas 9,11-epoxymethano and 9,11-epoxy-carbonyl PGH1 produced an inhibition of arachidonic acid-induced platelet aggregation. On isolated rabbit thoracic aorta strips, 9,11-epoxycarbonyl PGH1 showed strong contracting activity (5 times as active as 11,9-epoxy-methano PGH2 and 31 times as active as PGH2). All the analogs of PGH1 caused contraction of guinea pig tracheal muscle and caused an increase of perfusion pressure in guinea pig heart, though 11,9-epoxymethano and epoxy-carbonyl PGH1 were far more active than 9,11-epoxymethano and epoxycarbonyl PGH1. Differences in biological activities between 11,9-epoxymethano and epoxycarbonyl PGH1, and 9,11-epoxymethano and epoxycarbonyl PGH1 indicate that the orientation of functional groups at C9 and C11 influences biological activities. 相似文献
2.
The contractile response to three different prostanoids of the isolated human myometrium and the different layers of the utero-tubal junction (UTJ) was studied . The prostaglandin endoperoxide, PGH2, stimulated contractility of both the myometrium and the outer and inner muscle layers of the UTJ, whereas the intermediate layer of the UTJ was inhibited. Thromboxane A2 generated from PGH2 and a thromboxane synthase preparation caused a stimulation of both the myometrium and all three layers of the UTJ. The stimulatory response to TxA2 occurred at concentrations as low as 50–70 pg/ml. The sodium salt of PGI2 was found to relax both the myometrium and all the layers of the UTJ. Intravenous administration of PGI2 in repeated doses between 2–8 μg induced facial flushing and headache but had little if any effect on uterine contractility. At least under conditions, these short-lived prostanoids and/or their metabolites apparently have a specific action on uterine contractility, an action which is manifested at comparatively low concentrations. 相似文献
3.
Yuling Chi 《Biochemical and biophysical research communications》2010,395(2):168-172
Prostaglandin H2 not only serves as the common precursor of all other PGs, but also directly triggers signals (e.g. platelet aggregation), depending on its location and translocation. The prostaglandin carrier PGT mediates the transport of several prostanoids, such as PGE2, and PGF2α. Here we used PGT in the plasma membrane as a model system to test the hypothesis that PGT also transports PGH2. Using wild-type and PGT-expressing MDCK cells, we show that PGH2 uptake is mediated both by simple diffusion and by PGT. The PGH2 influx permeability coefficient for diffusion is (5.66 ± 0.63) × 10−6 cm/s. The kinetic parameters of PGH2 transport by PGT are Km = 376 ± 34 nM and Vmax = 210.2 ± 11.4 fmol/mg protein/s. PGH2 transport by PGT can be inhibited by excess PGE2 or by a PGT inhibitor. We conclude that PGT may play a role in transporting PGH2 across cellular membranes. 相似文献
4.
R.J. Gryglewski J.A. Salmon F.B. Ubatuba B.C. Weatherly S. Moncada J.R. Vane 《Prostaglandins & other lipid mediators》1979,18(3):453-478
In human platelet-rich plasma (PRP) eicosapentaenoic acid (EPA) inhibited platelet aggregation induced by a stable analogue of PGH2 (U46619), arachidonic acid, collagen or ADP. EPA was more potent than oleic, linoleic, α-linolenic or γ-linolenic acids. In aspirin-treated platelets, aggregation induced by U46619 was inhibited to a similar extent by arachidonic acid or by EPA over a range of concentrations of 0.05–0.3 mM. EPA incubated with PRP did not induce the generation of a thromboxane (TXA)-like activity; indeed it prevented the formation of TXA2 induced by arachidonic acid or by collagen. The anti-aggregatory activity of EPA was not influenced by inhibitors of cyclo-oxygenase and lipoxygenase. The anti-aggregatory action of EPA may be caused by a rapid occupancy by EPA of TXA2/PGH2 “receptors” on platelet membrane as well as by a slower displacement of arachidonic acid from platelet phospholipids by chemically unchanged molecules of EPA.Not all samples of PRP were irreversibly aggregated by PGH2, but in those that were, PGH3 also induced an immediate dose-dependent but reversible aggregation. After a 4 min incubation of non-aggregating doses of PGH2 or PGH3 (100–300 nM) with PRP a stable anti-aggregatory compound was detected. The inhibitory activity produced from PGH3 was apparently more potent (ca 10 times) than that obtained from PGH2. The anti-aggregating compounds were identified by TLC and GLC-MS as PGD2 and PGD3. The apparent difference of potency between PGD2 and PGD3 was attributed to the concurrent production of PGE2 and PGE3. PGE2 prevented the inhibitory effect of PGD2 whereas PGE3 did not affect the activity of PGD3.It is concluded that one of the reasons for the low incidence of myocardial infarction in Eskimos could be that the pro-aggregatory arachidonic acid is replaced in their phospholipids by the anti-aggregatory EPA. 相似文献
5.
Contractions of isolated iris sphincter muscles were measured in response to several free fatty acids, hydroperoxy and hydroxy derivatives of 20:3(n-3), 20:3(n-6) and 20:4, PGH2, and the epoxymethano methano analogs of PGH2. The free acids of prostaglandin precursors elicited comparatively strong contractions, hydroperoxy and hydroxy acids gave intermediate and nonspecific response whereas nonprostaglandin precursor acids elicited little response. PGH2 was 100 to 1000 times more effective than arachidonic acid or the epoxymethano analogs. The latter compounds inhibited the production of contractions by PGH2. These results allow an interpretation that the iris sphincter muscle contains an active thromboxane synthase and receptors for endoperoxide and thromboxane that initiate contraction. 相似文献
6.
G.A. Higgs S. Bunting S. Moncada J.R. Vane 《Prostaglandins & other lipid mediators》1976,12(5):749-757
Homogenates of phagocytosing polymorphonuclear leukocytes obtained from rabbit peritoneum were incubated with the prostaglandin endoperoxides PGG2 or PGH2. After 2 min at 0°C, incubation mixtures contained an increased rabbit aorta contracting activity. Ether extracts of incubation mixtures contained a substance which contracted the superfused strips of rabbit aorta and coeliac artery and had a half life which was similar to thromboxane A2. The generation of thromboxane A2-like activity from PG endoperoxides was prevented by boiling the homogenate prior to incubation, or by pretreatment with benzydamine, a drug which blocks thromboxane formation in platelets. Production of thromboxane A2-like material by leukocyte homogenates was compared with platelet microsomal thromboxane synthetase. 相似文献
7.
Ernst Wm. Spannhake Terry L. Adams Steven R. Kleeberger 《Prostaglandins & other lipid mediators》1985,30(6):1041-1055
The effects of repeated antigen exposure on the synthesis of mediators by lung tissues are not well understood. To investigate the influence of antigen challenge on the synthesis of prostaglandins by central airway and peripheral lung tissues, fourteen sensitive sheep underwent biweekly exposure to aerosolized antigen (7) or saline (7). Following the fifth exposure, microsomal and high speed supernatant fractions were prepared from trachealis muscle and lung parenchyma. Synthesis of thromboxane (TX) A2, prostaglandin (PG) D2 and PGI2 from the PG endoperoxide intermediate, PGH2, was assayed over a range of substrate concentrations from 3–200 uM. Synthesis of PGI2 by trachealis microsomes was approximately 5-fold greater than that of TXA2. PGI2 and TXA2 production was identical in tracheal preparations from Ascaris- and saline-exposed animals. In parenchymal tissues, where TXA2 production predominated over PGI2 by 9-fold, preparations from Ascaris- exposed animals synthesized 50% more TXA2 than controls at PGH2 concentrations of 25 uM and above, whereas synthesis of PGI2 and PGD2 were similar in preparations from both groups of animals. The density of pulmonary mast cells was decreased by 21% in the Ascaris group, whereas polymorphonuclear leukocyte density was unchanged. These results demonstrate the differential synthesis of TXA2 and PGI2 in central airways and peripheral lung regions of the sheep. They further indicate that repeated exposure of the airways to antigen selectively enhances TXA2 synthesis in the lung periphery of sensitized animals. The site of this increased enzymatic activity, whether in resident cells or newly-infiltrated cells, has not been determined. 相似文献
8.
Larry P. Feigen Barry M. Chapnick Robert R. Gorman Albert L. Hyman Philip J. Kadowitz 《Prostaglandins & other lipid mediators》1978,16(5):803-813
Effects of the prostaglandin endoperoxide, PGH2, were investigated in the renal and superior mesenteric vascular beds in anesthetized dogs. Vascular effects of a stable PGH2 analog were also studied in the intestine. Blood flow was measured with electromagnetic flowmeters and vasoactive hormones were administered by close intra-arterial injection. Authentic PGH2 increased blood flow in the kidney and intestine in a dose-related manner. Mesenteric blood flow was reduced by the PGH2 analog in a dose-dependent fashion which was similar to the vasoconstrictor activity of norepinephrine in this organ. PGH2 is biologically unstable and the type and activity of its metabolic products may vary in different regional vascular beds. Most of the known products of PGH2 metabolism in the kidney are vasodilators whereas in the intestine both vasodilator and vasoconstrictor metabolites are formed. It has been suggested that the vascular activity of PGH2 in an organ is dependent on the predominant type and activity of specific terminal enzymes that convert PGH2 to its various vaso-active products. 相似文献
9.
D.R. Smith B.C. Weatherly J.A. Salmon F.B. Ubatuba R.J. Gryglewski S. Moncada 《Prostaglandins & other lipid mediators》1979,18(3):423-438
PGH3 was biosynthesised from all-cis-5,8,11,14,17-eicosapentaenoic acid (20:5ω3) by an acetone-pentane powder of ram seminal vesicles and its structure was confirmed by GLC-MS after its reduction to PGF3α. PGH3 was transformed by horse platelet microsomes to TXB3, and by aortic microsomes to Δ17-6-keto-PGF1α. The structures of these compounds were confirmed by GLC-MS. 相似文献
10.
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
11.
Rat anterior pituitary explants were incubated with PGI2, PGH2 and PGE2 in the presence of theophylline (1mM) and the production of cyclic AMP was measured. PGE2 was found to be about 20 times more potent than PGI2 while PGH2 was slightly more effective than PGI2. The results suggest that PGI2 does not play a physiological role in cyclic AMP mediated events in the rat anterior pituitary. 相似文献
12.
Contractile responses to serotonin were examined in the longitudinal portal vein to determine whether such responses were mediated by the interaction of serotonin with 5HT1 receptors (those that preferentially bind [3H]serotonin) or 5HT2 receptors (those that preferentially bind [3H]spiperone). Using eight serotonin receptor antagonists (spiperone, metergoline, LY53857, ketanserin, trazodone, benzoctamine, 1-(1-naphthyl)piperazine, and 1-meta-methoxyphenylpiperazine), we found a significant correlation between the affinity for serotonin receptors in the rat portal vein and the ability to bind to 5HT2, but no 5HT1 receptors in rat frontal cortical membranes. Thus, the receptors mediating vascular contraction to serotonin in the rat portal vein were similar to those receptors defined in other vascular beds from the rat (aorta, jugular vein, and caudal artery). Furthermore, contraction resulting from the cumulative addition of serotonin in the rat portal vein was associated with desensitization (higher ED50 value) relative to contractions produced by the non-cumulative addition of serotonin. Affinities of serotonin receptor antagonists were also lower when determined by antagonism of cumulative serotonin concentration-response curves compared to affinities obtained by antagonism of non-cumulative concentration-response curves. Thus, 5HT2 receptor affinities of antagonists in the rat portal vein are best determined by the shift of non-cumulative responses to serotonin. 相似文献
13.
We have reported tha allicin, a constituent of garlic oil, has no effect on the activities of platelet cyclooxygenase or thromboxane synthase, or vascular PGI2 synthase. The effect of allicin on glutathione (GSH) dependent PGH2 to PGE2 isomerase is unknown. We therefore studied the effect of allicin on PGE2 biosynthesis in a murine mammary adenocarcinoma cell line (No 4526). Intact or sonicated cells were incubated with either 14C-arachidonic acid (AA) or 14C-PHG2, respectively. Following metabolism, products were extracted, separated by TLC and analyzed by radiochromatographic scan. PGE2 was predominantly formed with minimal amounts of PGF2α and PGD2. Formation of 6-keto-PGF1α or TXB2 was not detected indicating the absence of TXA2 and PGI2 synthase activity. Indomethacin and ibuprofen inhibited the PGE2 formation (p < 0.05). The enzymatic PGE2 formation in sonicates was blocked by depletion of the cellular non-protein thiols by buthionine sulfoximine and was shown to be dependent on GSH. Allicin, over the range of 10–1000 μM, inhibited the formation of PGE2 in cells exposed to 2.0 μM 14C-AA for 20 min. and in sonicated cells incubated with 20.0 μM 14C-PGH2 for 2 min (p < 0.05). Allicin did not alter cyclooexygenase-mediated oxygen utilization in ram seminal vessicle microsomes, suggesting that allicin selectively inhibits the GSH-dependent PGH2 to PGE2 isomerase in this adenocarcinoma cell line. 相似文献
14.
Prostaglandin H2 (PGH2) inhibited noradrenaline induced cyclic AMP accumulation in isolated rat fat cells in a dose-dependent manner. IC50 was 10 – 25 ng/ml both in the absence and in the presence of theophylline. The degree of inhibition produced by PGH2 increased with time of incubation. A stable PGH2 analog did not inhibit cyclic AMP accumulation. PGH2 was rapidly converted by isolated fat cells to PGD2, PGE2 and PGH2α, but no formation of thromboxane B2 was found either
or
. PGE2 was a more potent inhibitor than PGH2 of noradrenaline induced cyclic AMP accumulation. PGD2 enhanced cyclic AMP accumulation in a limited concentration interval, while PGF2α was essentially uneffective.Our results suggest that PGH2 is an inhibitor of cyclic AMP formation in isolated rat fat cells only after conversion to PGE2. A physiological role for PGH2 as a modulator of lipolysis is considered unlikely. 相似文献
15.
The binding characteristics of [3H]U46619 to washed human platelets were studied. [3H]U46619 binding to washed human platelets was saturable and displaceable. Kinetic studies yielded a Kd of 11 ± 4 nM (n=4). Scatchard analysis of equilibrium binding studies revealed one class of high affinity binding sites with a Kd of 20 ± 7nM and a Bmax of 9.1 ± 2.3 fmole/107 platelets (550 ± 141 binding sites per platelet) (n=4). A number of compounds that act as either agonists or antagonists of the TXA2/PGH2 receptor were tested for their ability to inhibit the binding of [3H]U46619 to washed human platelets. The Kds of the agonists and antagonists were similar to their potencies to induce or inhibit platelet aggregation. These data provide some evidence that [3H]U46619 binds to the putative human platelet TXA2/PGH2 receptor. 相似文献
16.
N.I. Ghali E.J. Kattelman S.C. Hung K.E. Schnorf G.C. Le Breton D.L. Venton 《Prostaglandins & other lipid mediators》1984,27(6):865-876
Because of its highly unstable nature, TXA2, produced by platelet metabolism of arachidonic acid, does not lend itself to use as a receptor probe for its own receptor. As such, the stable TXA2/PGH2 antagonist, trans-13-azaprostanoic acid (trans-13-APA, 12b), was prepared as the [17,18 3H] derivative ([3H] trans-13-APA, 12c) to study this receptor and to better evaluate the mechanism of action of these azaprostanoids. Tritiated trans-13-APA, 12c, was prepared in nearly theoretical specific activity (57 Ci/mmole) from (17z)-trans-13-azaprost-17-enoic acid (11b) by catalytic tritiation. The unsaturated 11b was prepared by condensation of cis-7-amino-3-heptene (8) with 2-(6-carboxyhexyl) cyclopentanone (9), NaBH4 reduction, chromatography, and hydrolysis of the trans isomer so isolated. The olefins 11a and b were also of biochemical interest because of the unsaturation in the lower side chain. The presence of similar unsaturation in PGH3 (4) and TXA3 (3) renders these prostaglandins inactive as proaggregatory agents. Evaluation of the antiaggregatory activity of 11a and b indicated it to be about the same potency in inhibiting human platelet aggregation as the parent cis and trans-13-APAs, suggesting that introduction of a double bond at the 17 position in platelet prostaglandin antagonists is unlikely to result in enhanced antiplatelet activity. 相似文献
17.
Robert R. Gorman Frank F. Sun Olga V. Miller Roy A. Johnson 《Prostaglandins & other lipid mediators》1977,13(6):1043-1053
An easy biochemical preparation of the prostaglandin endoperoxides, PGH1 and PGH2, is described. Both of the endoperoxides are potent contractors of isolated gerbil colon smooth muscle. Contracture with PGH2 is about equal to that caused by the standard, PGE1, while contracture with PGH1 is about half of that caused by PGE1. PGH1 was found to inhibit platelet aggregation induced by PGH2 and is about 1/10 as potent a stimulator of cAMP accumulation as is PGE1. The mass spectra of the methyl esters of both PGH1 and PGH2 were obtained, as were the infrared spectra of the two compounds. The nuclear magnetic resonance spectrum of PGH2 is characterized by signals at 4.58 δ and 4.47 δ for the C-9 and C-11 protons, respectively. 相似文献
18.
Lawrence Kent Charles J. Malemud Roland W. Moskowitz 《Prostaglandins & other lipid mediators》1980,19(3):391-406
The effects of two unsaturated fatty acids, prostaglandin E2, thromboxane B2 (TxB2) and 2 analogs of PG endoperoxide on monolayer cultures of rabbit articular chondrocytes have been studied. Arachidonic and linoleic acids had no effect on either DNA or sulfated-glycosaminoglycan biosynthesis, while 13,14 dihydro-PGE2 and PGE2 markedly inhibited the former. Two epoxymethano analogs of endoperoxide PGH2 (Em-PGH2) at concentrations of 2.5 and 25 μg/ml stimulated cell proliferation while reducing 35SO4 incorporation. By contrast, Em-PGH2 at lower concentrations (0.25 – 250 ng/ml) inhibited DNA synthesis in a dose-dependent manner. TxB2 at 2.5 μg/ml did not alter cellular proliferation. At lower concentrations, 2.5 and 25 ng/ml, TxB2 significantly stimulated sulfated-glycosaminoglycan biosynthesis in at least one of the chondrocyte populations tested. The results also demonstrated marked differences in the effects of TxB2 and the Em-PGH2 analogs on the partitioning of newly synthesized sulfated-proteoglycan between the cells and medium of these cell cultures. 相似文献
19.
Rat anterior pituitary explants were incubated with PGI2, PGH2 and PGE2 in the presence of theophylline (1mM) and the production of cyclic AMP was measured. PGE2 was found to be about 20 times more potent than PGI2 while PGH2 was slightly more effective than PGI2. The results suggest that PGI2 does not play a physiological role in cyclic AMP mediated events in the rat anterior pituitary. 相似文献
20.
The properties of beta-adrenoceptors in solubilised and particulate preparations of rat and rabbit lung have been assessed using the specific ligand (3H)-dihydroalprenolol ((3H)-DHA). Membranes were solubilised using the detergent digitonin and the specific binding of (3H)-DHA assayed using a charcoal-centrifugation technique to separate free and bound ligand. The equilibrium dissociation constant (KD) of specific (3H)-DHA binding was very similar in particulate and soluble preparations of rat and rabbit lung. Moreover, the optical isomers of propranolol displayed virtually identical stereospecific differences in soluble and membraneous preparations. However, the potency of various catecholamine agonists and the steepness of the displacement curves were greater in all solubilised preparations. Computer-assisted analysis of the displacement curves generated by the highly selective beta1 antagonist atenolol and the beta2 antagonist ICI 118.551, revealed the co-presence of beta1 and beta2 adrenoceptors in solubilised rabbit lung preparations. Furthermore, soluble beta1 adrenoceptors appear to be much more labile at 22°C than soluble beta2 adrenoceptors, providing support for the concept that these receptor subtypes are separate entities. 相似文献