共查询到20条相似文献,搜索用时 62 毫秒
1.
Christine G. Kuo Matthew T. Lewis Barbara A. Jakschik 《Prostaglandins & other lipid mediators》1984,28(6)
The homogenate of rat basophilic leukemia cells produces both the dihydroxy-leukotrienes and the peptido-leukotrienes (LT) C4, D4 and E4. The enzymes responsible for the formation of LTA4 and LTB4 are in the soluble fraction while the enzymes for LTC4, LTD4 and LTE4 are particulate (10, 000 × g pellet). Centrifugation of the 10, 000 × g pellet over a sucrose gradient resulted in two subfractions, a membrane fraction and a pellet (sucrose pellet.) The fractions were incubated with LTC4, and the products were identified by bioassay, HPLC and UV spectra. The membrane fraction contained the enzymes γ-glutamyl transpeptidase and amino peptidase which convert LTC4 to LTD4 and LTD4 to LTE4, respectively. When incubated with LTC4, the membrane fraction showed a dose dependent formation of LTD4 and a time course which reached a plateau at 30 to 45 minutes. Addition of serine borate blocked the formation of LTD4, and cysteine blocked LTE4. We conclude that the γ-glutamyl transpeptidase and the amino peptidase which produce LTD4 and LTE4 respectively are plasma membrane bound. 相似文献
2.
The novel metabolites of arachidonic acid, leukotriene (LT) A4, B4, C4, D4 and E4 have potent myotropic activity on guinea-pig lung parenchymal strip
. The receptors responsible for their action were characterized using desensitization experiments and the selective SRS-A antagonist, FPL-55712. During the continuous infusion of LTB4, the tissues became desensitized to LTB4 but were still responsive to histamine, LTA4, LTC4, LTD4 and LTE4. When LTD4 was infused continuously, the lung strips contracted to LTB4 and histamine but were no longer responsive to LTA4, LTC4, LTD4 and LTE4. Furthermore, FPL-55712 (10 ng ml−1− 10 ug ml−1) produced dose-dependent inhibitions of LTA4, LTC4, LTD4 and LTE4 without inhibiting the contraction to LTB4 and histamine. On the basis of these results, it appears that the guinea-pig lung parenchyma may have one type of receptor for LTB4 and another for LTD4; LTA4, LTC4 and LTE4 probably act on the LTD4 receptor. 相似文献
3.
The biological effects of leukotriene (LT)F4 were compared, on a molar basis, with those of LTC4, LTD4 and LTE4 on isolated superfused strips of guinea-pig ileum smooth muscle (GPISM) and lung parenchyma (GPP). LTF4 was 1–2 orders of magnitude less active than the other leukotrienes on GPISM (LTD4 > LTC4 > LTE4 > LTF4) whereas, in the GPP, the activity of LTF4 was comparable with that of LTE4, both leukotrienes being about one order of magnitude less active than LTC4 or LTD4 (LTC4=LTD4 > LTE4=LTF4). Further, LTF4 caused protracted contractions of the GPP which were indistinguishable from those due to LTE4 and of a much longer duration than responses elicited by either LTC4 or LTD4.FPL 55712 (1.9μM) antagonised actions of LTF4 in both tissue preparations. Indomethacin (2.8μM) inhibited contractions induced by LTF4 in GPP indicating that part of the bronchoconstriction due to LTF4, like that elicited by the other leukotrienes, is mediated via release of cyclo-oxygenase products. 相似文献
4.
The contractile activities of peptide leukotrienes (LT) on isolated spiral strips of ferret trachea were chracterized pharmacologically. LTC4 and LTD4 contracted ferret tracheal strips in a concentration-related manner and were 3- to 8-fold more potent than carbachol. In contrast, high concentrations of LTE4 evoked either weak contraction or none at all, whereas LTC4 and D4 were partial agonists compared to carbachol. In tissues which were unresponsive to LTE4, this compound antagonized contractile responses to LTC4 and D4 in an apparently competitive manner: Carbachol-induced contractions were not altered by LTE4. The cyclooxygenase inhibitor, indomethacin (5 μM), LT antagonists, FPL55712 (10 μM), atropine (1 μM), phenoxybenzamine (10 μM), and LTB4 (10 μM) failed to alter LTC4 and D4 concentration-response curves. The results in dicate that ferret trachea is sensitive to the contractile activity of LTC4 and LTD4 but not LTE4. The LT-induced contractions appear to be mediated by a direct action of the LT rather than indirectly through release of secondary mediators such as thromboxane, prostaglandin, or acetylcholine. LT receptors in ferret trachea are insensitive to FPL55712 but are antagonized by LTE4. 相似文献
5.
The effects of the 5-lipoxygenase inhibitors nordihydroguiaretic acid (NDGA), 5,8,11,14-eicosatetraynoic acid (ETYA), 1-phenyl-3-pyrazolidone (phenidone) and BW-755c, on the contractile response to LTC4 or LTD4 were examined on the isolated guinea pig trachea. Responses to either LTC4 or LTD4 or LTD4 were obtained on indomethacin treated tissues, in the presence of either L-serine-borate complex or L-cysteine, respectively, to exhibit metabolic conversion of the leukotrienes. NDGA (30 μM) and ETYA (100 μM) produced a selective competitive antagonism of LTD4 - induced contractions, while phenidone antagonized both LTC4- and LTD4 - induced responses in a non-competitive manner. In contrast, BW-755c (30 μM) did not significantly antagonize LTC4 or LTD4 concentration-response curves. The results suggest that leukotriene antagonism may be produced by large concentrations of some 5-lipoxygenase inhibitors. 相似文献
6.
In order to examine the modulation of leukotriene (LT) release, the PAF-acether-mediated stimulation of these compounds in rat lung was studied. Release of LTC4, LTD4 and LTE4 in both perfused and chopped lung preparations was measured using HPLC and radioimmunoassay. Pre-incubation or pre-infusion of the tissue with indomethacin and PGE2 was conducted to investigate the effect of cyclooxygenase inhibitors and products on the lipoxygenase pathway. In addition, the effects of LT levels of pre-incubation with vasoactive intenstinal polypeptide (VIP) in chopped lung were observed.In perfused rat lung, indomethacin reduced the levels of LTC4 relative to LTD4 as measured in the first 2 min after stimulation of the lung by PAF-acether. Chopped lung preparations, incubated for 15 min. exhibited higher levels of LTC4 and LTD4 in indomethacin-treated samples, this increases being effectively reversed by PGE2.In the VIP pre-incubation experiments clear inhibition of peptido -leukotriene synthesis was observed, with no LTC4 and only low levels of LTD4 and LTE4 observed in VIP-incubated samples. In preliminary experiments using rabbit C5a des arg and PAF-acether on rabbit lung parenchyma strips to stimulaet LT release, disodium cromoglycate pre-incubation was observed to inhibit this release.Inhibition of the 5-lipoxygenase pathway of PGE2 is supported by these experiments. VIP appears to act as an inhibitor of LTC4 and LTD4 biosynthesis or release in this model. Too little is known that peptidergic actions to postulate a mechanism by which a neuroendocrine peptide exerts control of release of arachidonate metabolites; however, VIP is associated with muscarinic stimulation (1) and has been found in mast cells (2). 相似文献
7.
In the presence of indomethacin, Leukotriene C4 (LTC4), LTD4 and LTE4 were shown to be contractile agents
on guinea pig gall bladder strips. The respective pD2 values for LTC4, LTD4 ad LTE4 were 9.1, 9.1 and 7.7. The contractile effects of LTD4 were not mediated through the generation of cyclooxygenase products and were antagonized by the SRS-A antagonist FPL-55712. The effects of PGE1, PGF2α, the endoperoxide analogue U44069 and histamine on gall bladder strips were also examined. All these agents caused dose-related contractions but were considerably less potent than the leukotrienes. Leukotrienes are therefore potent contractile agents on the guinea pig gall bladder and may contribute to gall bladder contractions or spasms
. 相似文献
8.
The biological actions of pure slow-reacting substance of anaphylaxis (SRS-A) from guinea-pig lung, pure slow-reacting substances (SRS) from rat basophilic leukaemia cells (RBL-1) and synthetic leukotrienes C4 (LTC4) and D4 (LTD4) have been investigated on lung tissue from guinea pig, rabbit and rat. In the guinea pig, the leukotrienes released cyclo-oxygenase products from the perfused lung and contracted strips of parenchyma. The effects of SRS-A, SRS and LTD4 were indistinguishable. LTC4 and LTD4 had similar actions although LTD4 was more potent than LTC4. Indo-methacin (1 μg/ml) inhibited the release of cyclo-oxygenase products from perfused guinea-pig lung and caused a marked reduction in contractions of guinea-pig parenchymal strips (GPP) due to LTC4 and LTD4. The residual contraction on the GPP was abolished by FPL 55712 (0.5 – 1.0 μg/ml). It appears, therefore, that a major part of the constrictor actions of LTC4 and LTD4 in guinea-pig lung are mediated by myotropic cyclo-oxygenase products, i.e. thromboxane A2 (TxA2) and prostaglandins (PGs).In rabbit and rat lung, however, SRS-A, SRS and the leukotrienes were much less potent in contracting parenchymal strips and there was little evidence of the release of cyclo-oxygenase products. FPL 55712 at a concentration of 1 μg/ml failed to antagonise leukotriene-induced contractions. 相似文献
9.
J.S. Fedyna D.W. Snyder D. Aharony D. Redkar-Brown R.D. Krell 《Prostaglandins & other lipid mediators》1990,39(5)
The actions of the peptide leukotriene (LT) LTC4, LTD4 and LTE4 and phenylephrine (PE) were studied in isolated left branches of the guiena-pig pulmonary artery (GPPA). Indomethacin 5 × 10−6 M enhanced both the potency and maximal response of all agonists, but the effect on LTD4 and LTE4 was larger. The influence of indomethacin suggests the release of an endogenous vasodilating cyclooxygenase product in GPPA. In the pressence of indomethacin the rank-order of potency was LTC4 > LTD4 > LTE4 ≥ PE with respective pD2 vaues of 7.65, 7.39, 6.35 and 6.26. All further studies were carried out in the presence of 5 × 10−6 indomethacin. Removal of the endothelium further increased both potency (> 3-fold) and the maximal response of all agonists tested, indicating that a non-clycooxygenase endothelium-dependent relaxing factor may be present in GPPA. In separate studies, GPPA was demonstrated capable of metabolizing 3H-LTC4 by an L-serine borate inhibitable γ-glutamyl transpeptidase. In contrast, relatively little formation of 3H-LTE4 was apparent either from 3H-LTC4 or 3H-LTD4. The LTD4-selective antagonists, LY 171,883 and ICI 198,615 had -log molar KB values of 6.07 ± 0.14 and 9.38 ± 0.32, respectively, against LTD4 in the absence of endothelium. The ability of LY 171,883 to antagonize LTC4 was eliminated in the presence of 45 mM serine borate in endothelium denuded tissues. LT receptors in GPPA appear to be heterogeneous and similar to guinea pig ariway receptors. 相似文献
10.
Cumulative dose-response curyes to leukotriene C4 (LTC4) and leukotriene D4 (LTD)4 were obtained on indomethacin (5 μM) treated isolated guinea pig tracheal spiral strips. LTC4 curves, in the presence of either glutathione (GSH; 10 mM) or L-serine borate (SB; 45 mM), were not antagonized by FPL-55712 (3 μM), a selective LTD4 receptor antagonist. LTC4 curves on trachea treated with a lower concentration of GSH (1 mM), and LTD4 curves were competitively antagonized by FPL-55712. LTC, curves on GSH (10 mM) treated trachea were 2 fold to the left of those on SB treated tissues. This effect of GSH was blocked by pretreatment with nordihydro-guiaretic acid (30 μM), an inhibitor of 5-lipoxygenase.GSH (10 μM) and SB (45 mM) are effective inhibitors of conversion of LTC4 into functionally important levels of LTD4 by the guinea pig trachea. In addition, GSH appeares to enhance LTC4 responsiveness by increasing synthesis of a contractile 5-lipoxygenase product(s), possibly LTC4. From the data it is suggested that for inhibition of LTC4 metabolism, SB may be more usefull when examining responses to exogenously applied LTC4, while GSH (10 mM) may be useful when examining responses to endogenously generated LTC4. 相似文献
11.
Pulmonary responses to intravenous leukotrienes C4, D4 and E4 administered as a bolus injection and by continuous infusion were studied in anesthetized guinea pigs. LTD4, LTC4 and LTE4 (respective ED50 of 0.21 ± .1, 0.64 ± .2 and 2.0 ± .1 μg kg−1) produced dose-dependent increases in insufflation pressure when given as a bolus injection to anesthetized guinea pigs (Konzett-Rössler). Bronchoconstriction was antagonized by FPL-55712 (50–200 μg kg−1), and indomethacin (50–200 μg kg−1) but was not significantly altered by mepyramine (1.0 mg kg−1), methysergide (0.1 mg kg−1), intal (10 mg kg−1) mepacrine (5 mg kg−1) or dexamethasone (10 mg kg−1). The beta adrenoceptor blocker, timolol (5 μg kg−1) produced a significantly greater potentiation of the responses to the leukotrienes than to arachidonic acid, histamine and acetylcholine. Responses to bolus injection of LTE4 but not LTD4 or LTC4 were partially antagonized by atropine (100 μg kg−1) and bilateral vagotomy. In experiments of a different design, continuous infusion of LTD4 and LTE4 (2.8–3.2 μg kg−1 min−1) into indomethacin-treated animals produced slowly developing increases in pulmonary resistance and decreases in compliance. The increase in resistance produced by LTE4 and LTD4 was partly reversed by intravenous FPL-55712 (1.0 mg kg−1) and atropine (100 μg kg−1) but was almost completely reversed by FPL-55712 (3 – 10 mg kg−1). These findings indicate that leukotrienes can produce bronchoconstriction in guinea pigs through cyclooxygenase-dependent and cyclooxygenase independent mechanisms both of which are blocked by FPL-55712. Cholinergic mechanisms are involved in the mediation of part of the response to bolus injection of LTE4 as well as a small part of the initial response to continuous infusion of LTD4 and LTE4. Intrinsic beta adrenoceptor activation serves to down modulate responses to the leukotrienes to a greater extent than responses to arachidonic acid, histamine and acetylcholine. 相似文献
12.
《Biochimica et Biophysica Acta (BBA)/Lipids and Lipid Metabolism》1994,1210(3):361-367
Human platelets are devoid of 5-lipoxygenase activity but convert exogenous leukotriene A4 (LTA4) either by a specific LTC4 synthase to leukotriene C4 or via a 12-lipoxygenase mediated reaction to lipoxins. Unstimulated platelets mainly produced LTC4, whereas only minor amounts of lipoxins were formed. Platelet activation with thrombin, collagen or ionophore A23187 increased the conversion of LTA4 to lipoxins and decreased the leukotriene production. Maximal effects were observed after incubation with ionophore A23187, which induced synthesis of comparable amounts of lipoxins and cysteinyl leukotrienes (LTC4, LTD4 and LTE4). Chelation of intra- and extracellular calcium with quin-2 and EDTA reversed the ionophore A23187-induced stimulation of lipoxin synthesis from LTA4 and inhibited the formation of 12-hydroxyeicosatetraenoic acid (12-HETE) from endogenous substrate. However, calcium did not affect the 12-lipoxygenase activity in the 100 000 × g supernatant of sonicated platelet suspensions. Furthermore, the stimulatory effect on lipoxin formation induced by platelet agonists could be mimicked in intact platelets by the addition of low concentrations of arachidonic acid, 12-hydroperoxyeicosatetraenoic acid (12-HPETE) or 13-hydroperoxyoctadecadienoic acid (13-HPODE). The results indicate that the elevated lipoxin synthesis during platelet activation is due to stimulated 12-lipoxygenase activity induced by endogenously formed 12-HPETE. 相似文献
13.
Jose Sraer Marcelle Bens Jean-Paul Oudinet Raymond Ardaillou 《Prostaglandins & other lipid mediators》1986,31(5)
Since leukotriene C4 (LTC4) may be locally synthesized by bone marrow-derived cells infiltrating the kidney in inflammatory renal diseases we examined the in vitro metabolism of exogenously added |3H| LTC4 by rat glomeruli and papilla using radiometric HPLC. Homogenized as well as intact glomeruli converted |3H| LTC4 mainly into |3h| LTE4 (83%) and, at a smaller extent, into |3H| LTD4 (4%). Intact |3H| LTC4 represented 13% of the sum of radioactive leukotrienes. Addition of L-cysteine resulted in accumulation of LTD4. In contrast, there was nearly no conversion of |3H| LTC4 (87% ntact) in the presence of homogenized papilla. The metabolism of |3H| LTC4 by the glomeruli was time- and temperature- dependent. The 10,000 g supernatant and pellet of homogenized glomeruli both retained the ability to metabolize |3H| LTC4. The papillary 10,000 g supernatant was inactive, as found for the total homogenate, whereas the papillary 10,000 g pellet separated from its supernatant could transform |3H| LTC4 into its metabolites, LTD4 and LTE4. Addition of increasing amounts of papillary 10,000 g supernatant to homogenized glomeruli progressively protected |3H| LTC4 from its bioconversion. These results demonstrate that both glomeruli and papilla possess the γ-glutamyl transpeptidase and dipeptidase necessary to process LTC4. However, the enzyme activity of the papilla is unmasked only when the inhibitor present in the 10,000 g supernatant is separated from the enzyme present in the pellet. 相似文献
14.
Clayton S. Spada Daivd F. Woodward Stephen B. Hawley Amelia L. Nieves 《Prostaglandins & other lipid mediators》1986,31(4):795-809
The ability of LTB4, LTC4, the 5S,6R and 5R,6S LTD4 stereoisomers, and LTE4 to evoke leukocyte infiltration into the conjunctiva was demonstrated in the guinea pig by histological andl ight microscopy techniques. LTD4 and LTE4 demonstrated a dose-dependent and predominantly eosinophilic infiltrate over the selected dose range (10ng to 1000ng), while there was only a minimal response to LTC4. LTB4 produced marked eosinophil inflitrates only at the highest dose; scattered neutrophil infiltrates were also noted at the high dose of LTB4. The 5R,6S LTD4 stereoisomer did not evoke any leukocyte infiltrantion. The SRS-A antagonist, FPL 55712, abolished pre-treatment had no inhibitory effect, indicating direct mediation of this response by LTs. Histamine caused a comparable eosinophilia over a dose range of 10μg to 1000μg. LT-induced eosinophil emigration was directed to the conjunctival epithelium; the cells appeared intact and no tissue damage was observed. These results may have relevance in the areas of allergic conjunctivitis and asthma research. 相似文献
15.
Huang SC 《Life sciences》2011,88(17-18):819-824
AimsLeukotriene D4 (LTD4) causes contraction of the stomach through unclear receptors. The aim of the present study is to characterize the cysteinyl leukotriene receptor (CysLT) mediating leukotriene-induced muscle contraction in the stomach.Main methodsWe measured contraction of gastric muscle strips isolated from the guinea pig fundus and antrum caused by cysteinyl leukotrienes, including LTC4, LTD4 and LTE4, as well as the dihydroxy leukotriene LTB4 in vitro.Key findingsIn both fundic and antral muscle strips, LTC4 and LTD4 caused marked whereas LTE4 caused moderate, concentration-dependent contractions. In contrast, LTB4 caused only small contraction. The relative potencies for cysteinyl leukotrienes to cause contraction in both fundus and antrum were LTC4 = LTD4 > LTE4. The LTD4-induced contraction was not affected by tetrodotoxin or atropine, suggesting that the action is not neurally mediated. The LTD4-induced contraction in the fundus was almost abolished by the CysLT1 selective antagonist montelukast. In contrast, the LTD4-induced contraction in the antrum was only partially inhibited by montelukast or the dual CysLT1 and CysLT2 antagonist BAY u9773. This antral contraction was almost abolished by the combination of montelukast and BAY u9773, indicating enhancement of inhibition.SignificanceThe results of the present study demonstrate that cysteinyl leukotrienes LTC4, LTD4 and LTE4 cause moderate to marked whereas the dihydroxy leukotriene LTB4 causes small muscle contraction in the stomach in vitro. The leukotriene-induced contraction is mediated by CysLT1 in fundus but by CysLT1 and CysLT2 in antrum. 相似文献
16.
Marcia E. Newcomer Nathaniel C. Gilbert 《The Journal of biological chemistry》2010,285(33):25109-25114
Leukotrienes (LTs), derived from arachidonic acid (AA) released from the membrane by the action of phospholipase A2, are potent lipid mediators of the inflammatory response. In 1983, Dahlén et al. demonstrated that LTC4, LTD4, and LTE4 mediate antigen-induced constriction of bronchi in tissue obtained from subjects with asthma (Dahlén, S. E., Hansson, G., Hedqvist, P., Björck, T., Granström, E., and Dahlén, B. (1983) Proc. Natl. Acad. Sci. U.S.A. 80, 1712–1716). Over the last 25+ years, substantial progress has been made in understanding how LTs exert their effects, and a broader appreciation for the numerous biological processes they mediate has emerged. LT biosynthesis is initiated by the action of 5-lipoxygenase (5-LOX), which catalyzes the transformation of AA to LTA4 in a two-step reaction. Ca2+ targets 5-LOX to the nuclear membrane, where it co-localizes with the 5-LOX-activating protein FLAP and, when present, the downstream enzyme LTC4 synthase, both transmembrane proteins. Crystal structures of the AA-metabolizing LOXs, LTC4 synthase, and FLAP combined with biochemical data provide a framework for understanding how subcellular organizations optimize the biosynthesis of these labile hydrophobic signaling compounds, which must navigate pathways that include both membrane and soluble enzymes. The insights these structures afford and the questions they engender are discussed in this minireview. 相似文献
17.
L.G. Letts M. Cirino P. Yusko B. Fitzsimonns A.W. Ford-Hutchinson J. Rokach 《Prostaglandins & other lipid mediators》1985,29(6):1049-1062
The actions of leukotrienes (LT'a) C4, D4, E4 and F4 have been investigated in the perfused hind-limb of the anesthetized pig. In the blood perfused hind limb LTC4, D4 and E4 increased the perfusion pressure in a dose-dependent fashion whereas LTF4 decreased perfusion pressure. In the Tyrode perfused hind limb all LT's increased perfusion pressure (rank order potency (LTC4 = LTD LTF4). The actions of LTF4 were not affected by a wide variety of pharmacological treatments, including indomethacin, methysergide and FPL-55712. The LT's aggregated porcine platelets (rank order potency LTC4 > LTF4 > LTD4) and induced the release of a platelet-derived vasodilatory mediator. The results provide pharmacological evidence of specific leukotriene receptors
and that leukotrienes can independently modulate blood flow. These data suggest that important interactions may occur between platelets, the arachidonate lipoxygenase products and platelet-derived substances in response to inflammatory stimuli in the cardiovascular system. 相似文献
18.
The actions of leukotriene (LT) C4 and D4 on the systemic arterial pressure and the insufflation pressure in guinea pigs and rabbits were examined. In guinea pigs, 0.3 – 3 nmole/kg of LTC4 and 0.1 – 1.0 nmole/kg of LTD4 administrated from left jugular vein caused dose-dependent increase of the airway resistance measured by the Konzett-Rössler method and a triphasic blood pressure response; an initial hypotension, a secondary hypertension and a third long-lasting hypotension. All of the hypertensive phase and 100 – 150% of the increase of the airway resistance by LTC4 and LTD4 were inhibited by a selective thromboxane synthetase inhibitor, OKY-1581 (10 mg/kg, i.v.) and only the hypertension was observed. Indomethacin (10 mg/kg, i.p.) also inhibited not only the airway resistance increase, but also the prolonged hypotension by LTC4 and shortened the duration of the hypotension by LTD4. It is suggested that thromboxane might be involved in bronchoconstriction and hypertensive effects by LTC4 and LTD4 and that hypotensive prostaglandin might be involved in the hypotensive phase after LTC4 and LTD4. In rabbits, the increse of the airway resistance by LTC4 and LTD4 (upto 100 nmole/kg, i.v.) was negligible and only the hypotension was observed. 相似文献
19.
H.L. Lippton W.M. Armstead A.L. Hyman P.J. Kadowitz 《Prostaglandins & other lipid mediators》1984,27(2):233-243
The effects of leukotriene C4 (LTC4) and leukotriene D4 (LTD4) in the feline mesenteric vascular bed were investigated under conditions of controlled blood flow so that changes in perfusion pressure directly reflect changes in vascular resistance. Intra-arterial injections of LTC4 and LTD4 (0.3–3.0 μg) increased perfusion pressure in a dose-related fashion. Vasoconstrictor responses to LTC4 and LTD4 were similar to norepinephrine (NE) whereas mesenteric vasoconstrictor response to the thromboxane analog, U46619, was markedly greater than were responses to LTC4 and LTD4. Meclofenamate in a dose that greatly attenuated the systemic depressor response to arachidonic acid was without effect on vasoconstrictor responses to LTC4 and LTD4, NE and U46619 in the mesenteric vascular bed. The present data show that LTC4 and LTD4 possess significant vasoconstrictor activity in the feline mesenteric vascular bed. In addition, the present data suggest that products of the cyclooxygenase pathway do not mediate vasoconstrictor responses to LTC4 and LTD4 in the intestinal circulation of the cat. 相似文献
20.
《Journal of molecular graphics》1995,13(6):337-341
Molecular dynamics simulations of leukotriene C4 (LTC4), leukotriene D4 (LTD4), and leukotriene E4 (LTE4) were carried out, and the data were visualized in an animated video format. Three-dimensional ghost images show the positions of the heavy atoms of all three molecules throughout the simulations. The ghost images can be superimposed to give a single three-dimensional image in which the shapes of the most populated conformers of each molecule are apparent and can be compared. Leukotriene D4 was found to occupy mostly T-shaped conformations, while LTC4 occupied mostly cup-shaped conformations, and LTE4 occupied a wide range of conformations spanning the LTD4 and LTC4 types. Digital filtering and graphing of the internal geometries of the molecules as a function of time revealed differences in dynamic behavior. The results are discussed in light of current knowledge about leukotriene receptors. 相似文献