Journal of lipid mediators最新文献_第3页

Platelet-activating factor (PAF)-induced cardiopulmonary dysfunctions and their reversal with a PAF antagonist (BN 52021) in strain 13 guinea pigs. 13株豚鼠血小板活化因子(PAF)诱导的心肺功能障碍及其与PAF拮抗剂(BN 52021)的逆转

Journal of lipid mediators Pub Date : 1993-07-01

C Qian, Z M Guo, C J Peters, C T Liu

{"title":"Platelet-activating factor (PAF)-induced cardiopulmonary dysfunctions and their reversal with a PAF antagonist (BN 52021) in strain 13 guinea pigs.","authors":"C Qian, Z M Guo, C J Peters, C T Liu","doi":"","DOIUrl":"","url":null,"abstract":"Cardiovascular and respiratory responses to a 2 h intravenous constant infusion of PAF (5 and 10 ng/kg per min) were studied in strain 13 guinea pigs. PAF decreased arterial blood pressure, left systolic ventricular pressure, and cardiac output (CO). These cardiovascular changes were dose-dependent. The PAF-induced hypotension returned to a pre-infusion level spontaneously with increased total peripheral resistance despite continuous infusion of PAF. The decreased CO was most striking, and did not recover to pre-infusion levels due to depressed cardiac contractility and impaired ventricular relaxation. Respiratory responses to PAF infusion at these doses were mild and only occurred after serious cardiovascular dysfunctions developed. A higher dose of PAF (20 ng/kg per min) produced drastically decreased CO and dynamic lung compliance (Cdyn), increased pulmonary airway resistance, hypoventilation and apnea within 10-40 min. BN 52021, a PAF receptor antagonist, administered as a single i.v. dose (6 mg/kg) 15 min after PAF infusion, reversed most of cardiopulmonary dysfunctions and prevented death by increasing cardiac contractility, CO, and minute volume from extremely low values. The data suggest that marked cardiopulmonary disturbances induced by intravenous PAF infusion reflects certain pathophysiological mechanisms of diseases that may involve the cellular release of PAF. The administration of BN 52021 or other potent PAF antagonists may be beneficial under these circumstances.","PeriodicalId":16323,"journal":{"name":"Journal of lipid mediators","volume":"7 3","pages":"223-37"},"PeriodicalIF":0.0,"publicationDate":"1993-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19208158","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 effect of heparin and related proteoglycans on allergen and PAF-induced eosinophil infiltration. 肝素及相关蛋白聚糖对变应原和paf诱导的嗜酸性粒细胞浸润的影响。

Journal of lipid mediators Pub Date : 1993-07-01

E A Seeds, J Hanss, C P Page

引用次数: 0

Labeling of the mitochondrial membrane D-3-hydroxybutyrate dehydrogenase (BDH) with new bifunctional phospholipid analogues. 新的双功能磷脂类似物标记线粒体膜d -3-羟基丁酸脱氢酶(BDH)。

Journal of lipid mediators Pub Date : 1993-06-01

B Nasser, C Morpain, J Zirkel, M Seiter, B Laude, W E Trommer, N Latruffe

{"title":"Labeling of the mitochondrial membrane D-3-hydroxybutyrate dehydrogenase (BDH) with new bifunctional phospholipid analogues.","authors":"B Nasser, C Morpain, J Zirkel, M Seiter, B Laude, W E Trommer, N Latruffe","doi":"","DOIUrl":"","url":null,"abstract":"D-3-Hydroxybutyrate dehydrogenase (BDH), an inner mitochondrial protein, is a well-known phospholipid dependent enzyme. It is a primary dehydrogenase of the oxidative phosphorylation system and is involved in the redox balance of the NAD+/NADH pool. The preparation of fluorescent phospholipids and newly synthesized bifunctional phospholipid analogues (fluorescent and photoactivatable) allowed us to study the structural requirement for lipid activation of the purified enzyme. This paper reports the chemical synthesis protocols to prepare these new phospholipids and their characterization. Illumination experiments of complexes between bifunctional phospholipids and BDH which lead to a cross-linked polypeptide indicate that both the polar head and the hydrophobic moiety of phospholipids interact with BDH. The bifunctional phospholipids were also tested on other lipid-binding proteins, i.e., horse cytochrome c and bovine serum albumin, and demonstrated the promising potential of this new type of photoactivatable molecules which can be followed merely by fluorescence without radioactive labeling.","PeriodicalId":16323,"journal":{"name":"Journal of lipid mediators","volume":"7 2","pages":"169-82"},"PeriodicalIF":0.0,"publicationDate":"1993-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19385751","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

MK 287: a potent, specific, and orally active receptor antagonist of platelet-activating factor. MK 287:一种有效的，特异性的，口服活性的血小板活化因子受体拮抗剂。

Journal of lipid mediators Pub Date : 1993-06-01

S B Hwang, M H Lam, D M Szalkowski, D E MacIntyre, T J Bach, S Luell, R Meuer, S P Sahoo, A W Alberts, J C Chabala

{"title":"MK 287: a potent, specific, and orally active receptor antagonist of platelet-activating factor.","authors":"S B Hwang, M H Lam, D M Szalkowski, D E MacIntyre, T J Bach, S Luell, R Meuer, S P Sahoo, A W Alberts, J C Chabala","doi":"","DOIUrl":"","url":null,"abstract":"MK 287 (L-680,573), a tetrahydrofuran analog, potently inhibited [3H]C18-PAF binding to human platelet, polymorphonuclear leukocyte (PMN) and lung membranes with K1 values of 6.1 +/- 1.5, 3.2 +/- 0.7, and 5.49 +/- 2.3 nM, respectively. The inhibitory effects are stereospecific and competitive. The racemate, L-668,750 is less potent and the enantiomer, L-680,574 is 20-fold less potent than MK 287. Inhibition of the binding of [3H]C18-PAF to human PMN membranes by MK 287 was associated with the reduction of the affinity of the radioligand but not the number of the receptor sites. Binding of other radioligands (e.g., LTB4, LTC4, C5a, FMLP) to their specific receptors was unaltered at 1-10 microM MK 287. [3H]MK 287 bound to membranes from human platelets and PMNs: KD = 2.1 +/- 0.6 and 2.9 +/- 1.2 nM, respectively. When examined on isolated human cells, MK 287 potently and selectively inhibited PAF-induced aggregation of platelets in plasma (ED50 = 56 +/- 38 nM) or gel-filtered platelets (ED50 = 1.5 +/- 0.5 nM) and elastase release from PMNs (ED50 = 4.4 +/- 2.6 nM). In studies in vivo, MK 287 inhibited PAF-induced lethality in mice (ED50 = 0.8 mg/kg orally) and PAF-induced bronchoconstriction in guinea pigs (ED50 = 0.18 mg/kg intraduodenally and 0.19 mg/kg intravenously). Inhibition of PAF-induced bronchoconstriction was accompanied by parallel rightward shifts in concentration-response curves for PAF-induced platelet aggregation measured ex vivo.","PeriodicalId":16323,"journal":{"name":"Journal of lipid mediators","volume":"7 2","pages":"115-34"},"PeriodicalIF":0.0,"publicationDate":"1993-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19385747","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

Lack of increase or reduction in circulating platelet factor 4 and heparin-releasable platelet factor 4 in symptomatic patients with asthma. 有症状哮喘患者循环血小板因子4和肝素释放血小板因子4缺乏升高或降低。

Journal of lipid mediators Pub Date : 1993-06-01

G Luzzatto, G Cella, P Boschetto, L Fabbri

引用次数: 0

Occupancy of platelet receptors for platelet-activating factor in asthmatic patients during an allergen-induced bronchoconstrictive reaction. 哮喘患者在过敏原诱导的支气管收缩反应中血小板活化因子受体的占用。

Journal of lipid mediators Pub Date : 1993-06-01

J A Burgers, P L Bruynzeel, H J Mengelers, J Kreukniet, J W Akkerman

{"title":"Occupancy of platelet receptors for platelet-activating factor in asthmatic patients during an allergen-induced bronchoconstrictive reaction.","authors":"J A Burgers, P L Bruynzeel, H J Mengelers, J Kreukniet, J W Akkerman","doi":"","DOIUrl":"","url":null,"abstract":"The administration of platelet-activating factor (PAF) to human subjects triggers asthma-like responses. We investigated whether a bronchoconstrictive reaction was accompanied by the release of PAF in the circulation of allergic asthmatics. The appearance of PAF was assessed by measuring the number of freely accessible PAF-receptors on platelets in vitro, assuming that the contact between platelets and PAF in vivo would reduce the receptor binding of [3H]PAF in vitro. 16 asthmatics were challenged twice, first with buffer and the next day with allergen. A comparison between receptor binding after provocation with the data of the same patients after allergen challenge revealed a significant difference in PAF binding (P = 0.034), with an average decrease of 14% immediately after allergen challenge followed by a return to control values after about 4 h and a transient increase of 9% at 7 h after provocation. The decrease in accessible PAF receptors was accompanied by a slight decrease in platelet count in peripheral blood between 30 min and 4 h after allergen challenge. The platelet counts recovered to the original values afterwards. These data support the concept that in patients with allergic asthma PAF is secreted in the circulation. The contact between PAF and the platelets may trigger the transient sequestration of platelets, possibly in the lung. Thus, PAF and platelets may contribute to the pathogenesis of allergic asthma.","PeriodicalId":16323,"journal":{"name":"Journal of lipid mediators","volume":"7 2","pages":"135-49"},"PeriodicalIF":0.0,"publicationDate":"1993-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19385748","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

Protective effects of PF-10040 in experimental NSAID-gastritis: role of leukocytes, leukotrienes and PAF. PF-10040对实验性nsaid -胃炎的保护作用:白细胞、白三烯和PAF的作用。

Journal of lipid mediators Pub Date : 1993-06-01

J L Wallace, G W McKnight, D Donigi-Gale, T S Shoupe, D N Granger

{"title":"Protective effects of PF-10040 in experimental NSAID-gastritis: role of leukocytes, leukotrienes and PAF.","authors":"J L Wallace, G W McKnight, D Donigi-Gale, T S Shoupe, D N Granger","doi":"","DOIUrl":"","url":null,"abstract":"The effects and mechanism of action of PF-10040, a quinoline derivative, were examined in an experimental model of NSAID-gastritis. Oral pretreatment with PF-10040 dose-dependently reduced the severity of indomethacin-induced gastric damage, with a significant protective effect being observed with doses of 10 mg/kg or greater. The protective effects of this compound persisted for as long as 6 h after administration. PF-10040 also significantly reduced the severity of aspirin- or naproxen-induced gastric damage. At protective doses, PF-10040 did not significantly affect gastric LTB4 synthesis, LTB4-induced granulocyte recruitment to intradermal injection sites, or LTD4-induced changes in gastric blood flow. The free radical scavenging effects of PF-10040 were examined using an in vitro assay, in which it failed to exert significant effects at concentrations of up to 10 mM. PF-10040 had no significant effect on gastric acid secretion. In rat mesenteric venules, PF-10040 inhibited PAF-, but not LTB4-induced leukocyte adherence and emigration. These results suggest that the protective effects of PF-10040 are not attributable to scavenging of free radicals, inhibition of leukotriene synthesis, blockade of LTB4 or LTD4 receptors or inhibition of LTB4-mediated leukocyte endothelial cell adhesion.","PeriodicalId":16323,"journal":{"name":"Journal of lipid mediators","volume":"7 2","pages":"183-96"},"PeriodicalIF":0.0,"publicationDate":"1993-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19385752","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

Regulation of phospholipid metabolism by K+ channel blockers and inhibitors of choline transport in the Jurkat T cell line. Relationships with cell proliferation and interleukin-2 production. K+通道阻滞剂和胆碱转运抑制剂对Jurkat T细胞系磷脂代谢的调节。与细胞增殖和白细胞介素-2产生的关系。

Journal of lipid mediators Pub Date : 1993-06-01

C Aussel, N Cattan, C Pelassy, B Rossi

{"title":"Regulation of phospholipid metabolism by K+ channel blockers and inhibitors of choline transport in the Jurkat T cell line. Relationships with cell proliferation and interleukin-2 production.","authors":"C Aussel, N Cattan, C Pelassy, B Rossi","doi":"","DOIUrl":"","url":null,"abstract":"In the human T cell line Jurkat, three drugs generally used as effectors of K+ channels, i.e., quinine, 4-aminopyridine and tetraethylammonium, modify phospholipid metabolism. The drugs inhibited the synthesis of both phosphatidylcholine and phosphatidylethanolamine. The mechanism of such inhibition involves a decreased uptake of choline and ethanolamine by the cells, since the three K+ channel blockers were found to be able to competitively inhibit the high-affinity choline/ethanolamine transport system at the membrane level. In contrast, choline transport-inhibitors such as hemicholinium-3, decamethonium and dodecyltrimethylammonium do not inhibit interleukin-2 synthesis and proliferation of the Jurkat T cell line. This indicates that the inhibition of either phosphatidylcholine and/or phosphatidylethanolamine synthesis is not directly implicated in these processes. The inhibition of interleukin-2 synthesis appeared to be mediated through the inhibition of diacylglycerol production induced by T cell activators. A major role for phosphatidylserine in the regulation of T cell activation emerged, since we demonstrated that a panel of K+ channel blockers enhanced the synthesis of this phospholipid mimicking the previously described effect of exogenously added phosphatidylserine in Jurkat cells, i.e., a blockade of interleukin-2 synthesis probably due to a defect in diacylglycerol production.","PeriodicalId":16323,"journal":{"name":"Journal of lipid mediators","volume":"7 2","pages":"99-113"},"PeriodicalIF":0.0,"publicationDate":"1993-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19385753","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

Isolation and identification of lysophosphatidylcholines as endogenous modulators of thromboxane receptors. 溶磷脂酰胆碱作为内源性血栓素受体调节剂的分离与鉴定。

Journal of lipid mediators Pub Date : 1993-06-01

D W Phillipson, A A Tymiak, J G Tuttle, K S Hartl, T W Harper, M S Bolgar, G T Allen, M L Ogletree

{"title":"Isolation and identification of lysophosphatidylcholines as endogenous modulators of thromboxane receptors.","authors":"D W Phillipson, A A Tymiak, J G Tuttle, K S Hartl, T W Harper, M S Bolgar, G T Allen, M L Ogletree","doi":"","DOIUrl":"","url":null,"abstract":"Inhibition of thromboxane receptor radioligand binding to human platelet membranes has been employed as the basis for a radioreceptor assay designed to measure thromboxane receptor binding activity in samples of biological fluids. This method was used during phase 1 clinical evaluation of the thromboxane receptor antagonist SQ 30,741. Frequently, baseline plasma samples as well as plasma samples from placebo-treated subjects showed significant inhibition of radioligand binding in the radioreceptor assay, suggesting the presence of endogenous thromboxane receptor ligands. This receptor binding activity was stable and could be monitored in blood from normal volunteers using a modification of the radioreceptor assay. In order to identify the substance responsible for the observed activity, the activity present in pooled bovine blood was isolated and evaluated by a combination of FAB/MS, 1H-NMR, 13C-NMR and co-injection with reference standards on HPLC. Several endogenous thromboxane receptor ligands were identified as L-alpha-lysophosphatidylcholine (LPC) species. One major species, palmitoyl-LPC, contracted isolated rat aortic spirals, and these contractions could be delayed or prevented, but not reversed by the thromboxane receptor antagonist SQ 29,548. Palmitoyl-LPC slightly potentiated aortic contractions induced by the thromboxane receptor agonist, U-46,619, and diminished in a concentration-dependent manner the antagonism by SQ 29,548 of contractile responses to U-46,619. These findings are consistent with a potential for LPC species to bind and activate thromboxane receptors.","PeriodicalId":16323,"journal":{"name":"Journal of lipid mediators","volume":"7 2","pages":"155-67"},"PeriodicalIF":0.0,"publicationDate":"1993-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19385750","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

Involvement of platelet-activating factor (PAF) in endotoxin- or ischaemia-induced intestinal hyperpermeability in the rat. 血小板活化因子(PAF)参与内毒素或缺血诱导的大鼠肠道高通透性。

Journal of lipid mediators Pub Date : 1993-05-01

J P Defaux, F Thonier, N Baroggi, A Etienne, P Braquet

引用次数: 0