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Journal of lipid mediators最新文献

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Effect of leukotrienes on sheep airway smooth muscle. 白三烯对绵羊气道平滑肌的影响。
Journal of lipid mediators Pub Date : 1993-05-01
Y Ishihara, J Sheller
{"title":"Effect of leukotrienes on sheep airway smooth muscle.","authors":"Y Ishihara,&nbsp;J Sheller","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The effects of leukotrienes (LT) C4, LTD4, LTE4 and LTB4 on the development of isometric tension by sheep airway smooth muscle were determined in a tissue bath. LTE4 (1.5 x 10(-7) M) had no contractile effect. LTB4 contracted only lung parenchymal strips. LTC4 (8 x 10(-8) M) and LTD4 (1.1 x 10(-7) M) caused contractions in trachea, bronchi and lung parenchyma that developed slowly and persisted. The tracheal contractions caused by LTD4 and ACh were potentiated approx. 30% by the cyclooxygenase inhibitor meclofenamate (10(-6) M). Meclofenamate had no effect on leukotriene induced contractions in bronchi or lung parenchymal strips. The bronchodilator prostaglandins PGI2 and PGE2 were released from sheep trachea at rest and after contraction by LTD4. Inhibition of their release by meclofenamate may explain the potentiation of LTD4 contractions by meclofenamate. In vitro, LTD4 and LTC4 have potent contractile effects on sheep airway smooth muscle that are not mediated by the secondary release of constrictor cyclooxygenase products. These leukotrienes may play a substantial role in the pathogenesis of allergen and endotoxin induced lung mechanics changes in sheep.</p>","PeriodicalId":16323,"journal":{"name":"Journal of lipid mediators","volume":"7 1","pages":"47-56"},"PeriodicalIF":0.0,"publicationDate":"1993-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19344154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effect of SR 27417 on the binding of [3H]PAF to rabbit and human platelets and human polymorphonuclear leukocytes. sr27417对[3H]PAF与家兔和人血小板及人多形核白细胞结合的影响
Journal of lipid mediators Pub Date : 1993-05-01
J M Herbert, M C Laplace, C Cailleau, J P Maffrand
{"title":"Effect of SR 27417 on the binding of [3H]PAF to rabbit and human platelets and human polymorphonuclear leukocytes.","authors":"J M Herbert,&nbsp;M C Laplace,&nbsp;C Cailleau,&nbsp;J P Maffrand","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>SR 27417, the first member of a newly developed PAF antagonist series, fully and competitively displaced [3H]PAF from its high-affinity binding sites on washed rabbit and human platelets with Ki values of 57 +/- 0.02 and 50 +/- 0.8 pM (n = 3), respectively. Studies carried out in parallel demonstrated that SR 27417 was 5-7-times more potent than C16-PAF itself and more than 50-60-fold as active as the best synthetic PAF antagonist yet described. Additionally, SR 27417 selectively and competitively inhibited the specific binding of [3H]WEB-2086, a selective PAF receptor antagonist to its high-affinity receptors on washed rabbit platelets (IC50 = 0.18 +/- 0.01 nM). On human polymorphonuclear leukocytes, [3H]PAF bound to two classes of specific binding sites with high (KD = 0.31 +/- 0.05 nM; Bmax = 1.2 +/- 0.07 fmol/10(6) cells) and low affinity (KD = 11.1 +/- 1.5 nM; Bmax = 13.7 +/- 0.8 fmol/10(6) cells). On these cells, SR 27417 selectively inhibited the specific binding of [3H]PAF to its high- and low-affinity receptors (IC50 values of 0.17 +/- 0.02 and 6.9 +/- 0.7 nM, respectively) and displayed the same inhibitory pattern as that already reported on platelets. In conclusion, SR 27417 can be considered as the most potent PAF receptor antagonist described to date.</p>","PeriodicalId":16323,"journal":{"name":"Journal of lipid mediators","volume":"7 1","pages":"57-78"},"PeriodicalIF":0.0,"publicationDate":"1993-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19379907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Leukotriene synthesis in U937 cells expressing recombinant 5-lipoxygenase. 表达重组5-脂氧合酶的U937细胞合成白三烯
Journal of lipid mediators Pub Date : 1993-05-01
S Kargman, P Rousseau, G K Reid, C A Rouzer, J A Mancini, E Rands, R A Dixon, R E Diehl, C Léveillé, D Nathaniel
{"title":"Leukotriene synthesis in U937 cells expressing recombinant 5-lipoxygenase.","authors":"S Kargman,&nbsp;P Rousseau,&nbsp;G K Reid,&nbsp;C A Rouzer,&nbsp;J A Mancini,&nbsp;E Rands,&nbsp;R A Dixon,&nbsp;R E Diehl,&nbsp;C Léveillé,&nbsp;D Nathaniel","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The U937 human promyelocytic cell line does not express 5-lipoxygenase, but does express 5-lipoxygenase-activating protein (FLAP). U937 cells do not synthesize leukotrienes after stimulation by calcium ionophore A23187. Dimethyl sulfoxide (DMSO) differentiation of U937 cells, towards a more mature monocyte-macrophage lineage, induces the expression of FLAP but not 5-lipoxygenase. These DMSO-differentiated U937 cells also lack the ability to synthesize leukotrienes. We infected viral RNA coding for 5-lipoxygenase into U937 cells using a retroviral vector and measured the synthesis of 5-lipoxygenase, FLAP, leukotrienes and 5-hydroxyeicosatetraenoic acid (5-HETE) by these cells after stimulation with A23187. Undifferentiated U937 cells infected with 5-lipoxygenase RNA expressed 5-lipoxygenase and FLAP but neither leukotrienes nor 5-HETE were detected after these cells were stimulated with A23187. Exposure of the 5-lipoxygenase-infected U937 cells to DMSO increased the expression of 5-lipoxygenase and FLAP, and these cells produced leukotrienes and 5-HETE in response to A23187. The synthesis of these products was inhibited by MK-886, a compound which specifically binds to FLAP.</p>","PeriodicalId":16323,"journal":{"name":"Journal of lipid mediators","volume":"7 1","pages":"31-45"},"PeriodicalIF":0.0,"publicationDate":"1993-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19344152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Tulopafant, a PAF receptor antagonist, increases capillary patency and prolongs survival in discordant cardiac xenotransplants. 图洛帕方是一种PAF受体拮抗剂，可增加毛细血管通畅，延长异种心脏移植患者的生存期。
Journal of lipid mediators Pub Date : 1993-05-01
D P O'Hair, A M Roza, R Komorowski, G Moore, R P McManus, C P Johnson, M B Adams, G M Pieper
{"title":"Tulopafant, a PAF receptor antagonist, increases capillary patency and prolongs survival in discordant cardiac xenotransplants.","authors":"D P O'Hair,&nbsp;A M Roza,&nbsp;R Komorowski,&nbsp;G Moore,&nbsp;R P McManus,&nbsp;C P Johnson,&nbsp;M B Adams,&nbsp;G M Pieper","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Hyperacute rejection is a serious complication of xenogeneic organ transplantation. It is believed that platelets play a pivotal role in this phenomenon. In this study, we provide the first known evidence of the efficacy of the PAF receptor antagonist, tulopafant, in improvement in graft function and histology of discordant cardiac xenografts. Transplantation of guinea pig hearts into recipient rats resulted in hyperacute rejection. Pretreatment of recipient animals with tulopafant (but not indomethacin) extended rejection time by 4-5-fold. Histological examination revealed marked diminution of both interstitial hemorrhage and deposition of platelet and granulocytes in capillaries of cardiac xenografts when recipient animals were pretreated with tulopafant.</p>","PeriodicalId":16323,"journal":{"name":"Journal of lipid mediators","volume":"7 1","pages":"79-84"},"PeriodicalIF":0.0,"publicationDate":"1993-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19379910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pharmacological profile of epiyangambin: a furofuran lignan with PAF antagonist activity. epiyangambin的药理学特征:具有PAF拮抗剂活性的呋喃木脂素。
Journal of lipid mediators Pub Date : 1993-05-01
H C Castro-Faria-Neto, M A Martins, P M Silva, P T Bozza, H N Cruz, M de Queiroz-Paulo, M A Kaplan, R S Cordeiro
{"title":"Pharmacological profile of epiyangambin: a furofuran lignan with PAF antagonist activity.","authors":"H C Castro-Faria-Neto,&nbsp;M A Martins,&nbsp;P M Silva,&nbsp;P T Bozza,&nbsp;H N Cruz,&nbsp;M de Queiroz-Paulo,&nbsp;M A Kaplan,&nbsp;R S Cordeiro","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The ability of a furofuran lignan, epiyangambin, to inhibit PAF-induced rabbit platelet aggregation in vitro and thrombocytopenia in rats was investigated. Epiyangambin dose-dependently inhibited PAF-induced platelet aggregation without modifying the amplitude of the maximal response, indicating a competitive antagonism. The IC50 value of epiyangambin for 10(-9) M PAF-induced aggregation was 6.1 x 10(-7) M and the Schild analysis provided a pA2 of 6.91 +/- 0.2 with a slope of 0.98 +/- 0.25 (n = 4) and a pKb of 6.94 +/- 0.19. Epiyangambin had no effect upon the platelet aggregation induced by collagen, thrombin or ADP. The in vivo administration of the lignan at 20 mg/kg significantly inhibited PAF-induced thrombocytopenia in rats. These data indicate that epiyangambin is a potent and selective antagonist of PAF both in vitro and in vivo.</p>","PeriodicalId":16323,"journal":{"name":"Journal of lipid mediators","volume":"7 1","pages":"1-9"},"PeriodicalIF":0.0,"publicationDate":"1993-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19343509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Stimulation of PGE2 synthesis in a co-culture of periosteal fibroblasts and osteoblast-like cells by parathyroid hormone. 甲状旁腺激素对骨膜成纤维细胞和成骨细胞样细胞共培养中PGE2合成的刺激作用。
Journal of lipid mediators Pub Date : 1993-05-01
C Y Yang, C L Meng
{"title":"Stimulation of PGE2 synthesis in a co-culture of periosteal fibroblasts and osteoblast-like cells by parathyroid hormone.","authors":"C Y Yang,&nbsp;C L Meng","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In previous experiments, we demonstrated that hPTH 1-34 activates PGE2 synthesis and calcium mobilization by chick calvaria. In this report, we started to search for the PTH responsible cell population in this bone tissue. When the chick calvariae were subjected to sequential enzyme digestion, we found that the third cell population were the cells that reacted to human PTH 1-34 and bovine PTH 1-34. A subsequent procedure was performed using the cells isolated from enzyme digestion and separated into two distinct populations--periosteal fibroblasts (PF) and osteoblast-like cells (OB)--by a two-step density gradient of Percoll. We found that PF and OB cells alone did not respond to PTH in terms of PGE2 synthesis. However, when these two cell populations were mixed in the proportion of 50:50, the synthesis of PGE2 and PGF2 alpha was increased significantly by the treatment of PTH and calcitonin. No effects were demonstrated in the mixing proportions of 30:70 and 70:30. These results suggest that PTH responsiveness may need a local interaction between periosteal fibroblasts and osteoblast-like cells residing in chick calvaria.</p>","PeriodicalId":16323,"journal":{"name":"Journal of lipid mediators","volume":"7 1","pages":"23-30"},"PeriodicalIF":0.0,"publicationDate":"1993-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19344151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Activation of phospholipases D and A by amphiphilic cations of cultured LA-N-2 cells is G protein- and protein kinase C-independent. 两亲性阳离子对培养的LA-N-2细胞的磷脂酶D和A的激活与G蛋白和蛋白激酶c无关。
Journal of lipid mediators Pub Date : 1993-05-01
I N Singh, R Massarelli, J N Kanfer
{"title":"Activation of phospholipases D and A by amphiphilic cations of cultured LA-N-2 cells is G protein- and protein kinase C-independent.","authors":"I N Singh,&nbsp;R Massarelli,&nbsp;J N Kanfer","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Several amphiphilic cations such as mepacrine, desipramine, didodecyldimethylamine, chlorpromazine, oleylamine and W-7 activated the phospholipase D (PLD) activity of cultured LA-N-2 cells. These compounds, except for oleylamine, provoked the release of fatty acids, suggesting phospholipase A activation. Melittin, a PLA2 stimulator, caused the robust release of the free fatty acids but was a poor PLD activator. Although PLD could be activated by GTP gamma S, the stimulation by these amphiphilic cations was not abolished by GDP beta S, an inhibitor of G protein function. There was no change in the PLD activation by these amphiphilic cations by DiC8, a PKC activator, or by H-7, a PKC inhibitor or in PKC down-regulated cells.</p>","PeriodicalId":16323,"journal":{"name":"Journal of lipid mediators","volume":"7 1","pages":"85-96"},"PeriodicalIF":0.0,"publicationDate":"1993-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19344155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The ocular effects of prostaglandins and the therapeutic potential of a new PGF2 alpha analog, PhXA41 (latanoprost), for glaucoma management. 前列腺素的眼部作用和一种新的PGF2 α类似物PhXA41 (latanoprost)在青光眼治疗中的治疗潜力
Journal of lipid mediators Pub Date : 1993-03-01
L Z Bito, J Stjernschantz, B Resul, O C Miranda, S Basu
{"title":"The ocular effects of prostaglandins and the therapeutic potential of a new PGF2 alpha analog, PhXA41 (latanoprost), for glaucoma management.","authors":"L Z Bito,&nbsp;J Stjernschantz,&nbsp;B Resul,&nbsp;O C Miranda,&nbsp;S Basu","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In the early days of prostaglandin (PG) research, the infusion of large PG doses into rabbit eyes already traumatized by cannulation, led to the conclusion that PGs have a profound ocular hypertensive effect that is associated with a breakdown of the blood-aqueous barrier. In contrast, repeated topical application of PGs to nontraumatized eyes of several species other than rabbits has later been shown to yield a maintained ocular hypotensive effect, without barrier breakdown. Due to its excellent pharmacokinetic properties, the isopropyl ester form of PGF2 alpha (PGF2 alpha-IE) is a much more potent ocular hypotensive agent and appeared to be better suited for the management of glaucoma, than PGF2 alpha itself or any currently used glaucoma drug. However, even this prodrug caused clinically unacceptable foreign-body sensation and conjunctival hyperemia, which could be reduced, or eliminated, only by some modifications of the omega chain of PGF2 alpha-IE. One such analog, PhXA41, maintained highly significant IOP reduction in glaucoma patients even with once-daily application at the remarkably low concentration of 0.006%. Because PhXA41 reaches intraocular tissues and the systemic circulation in its de-esterified free-acid form, which is a good substrate for the PG transport system, it retains the most important pharmacokinetic advantages of topically applied PGF2 alpha-IE. However, its greatly reduced side effects give PhXA41 a clear therapeutic advantage over PGF2 alpha-IE, making it an effective new drug candidate for the long-term medical management of glaucoma.</p>","PeriodicalId":16323,"journal":{"name":"Journal of lipid mediators","volume":"6 1-3","pages":"535-43"},"PeriodicalIF":0.0,"publicationDate":"1993-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19343508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A new class of leukotriene biosynthesis inhibitor: the development of MK-0591. 一类新的白三烯生物合成抑制剂:MK-0591的研制。
Journal of lipid mediators Pub Date : 1993-03-01
P Prasit, M Belley, M Blouin, C Brideau, C Chan, S Charleson, J F Evans, R Frenette, J Y Gauthier, J Guay
{"title":"A new class of leukotriene biosynthesis inhibitor: the development of MK-0591.","authors":"P Prasit,&nbsp;M Belley,&nbsp;M Blouin,&nbsp;C Brideau,&nbsp;C Chan,&nbsp;S Charleson,&nbsp;J F Evans,&nbsp;R Frenette,&nbsp;J Y Gauthier,&nbsp;J Guay","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The evolution of MK-0591 (3-[1-(4-chlorobenzyl)-3-(t-butylthio)-5-(quinolin-2-ylmethoxy+ ++)indol-2-yl]- 2,2-dimethylpropanoic acid), 12, a potent, orally active leukotriene biosynthesis inhibitor is described. MK-0591 is currently undergoing clinical evaluation as a potential agent for the treatment of asthma and inflammatory bowel disease. It acts through a novel mechanism by a specific interaction with a membrane protein, 5-lipoxygenase activating protein (FLAP), which has been shown to be essential for LT synthesis in inflammatory cells. A brief comparison of its biological activity with that of its progenitors MK-886 and L-674,636 is described.</p>","PeriodicalId":16323,"journal":{"name":"Journal of lipid mediators","volume":"6 1-3","pages":"239-44"},"PeriodicalIF":0.0,"publicationDate":"1993-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19344400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Thromboxane biosynthesis and metabolism in cardiovascular and renal disease. 血栓素在心血管和肾脏疾病中的生物合成和代谢。
Journal of lipid mediators Pub Date : 1993-03-01
C Patrono, P Patrignani, G Daví
{"title":"Thromboxane biosynthesis and metabolism in cardiovascular and renal disease.","authors":"C Patrono,&nbsp;P Patrignani,&nbsp;G Daví","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":16323,"journal":{"name":"Journal of lipid mediators","volume":"6 1-3","pages":"411-5"},"PeriodicalIF":0.0,"publicationDate":"1993-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19344976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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