{"title":"The prostacyclin analogues, cicaprost and iloprost, increase cytosolic Ca2+ concentration in the human erythroleukemia cell line, HEL, via pertussis toxin-insensitive G-proteins.","authors":"I Schwaner, R Seifert, G Schultz","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In the human erythroleukemia cell line, HEL, prostaglandin E2 (PGE2) and the stable prostacyclin analogue, iloprost, increase cytosolic Ca2+ concentration ([Ca2+]i) via pertussis toxin-sensitive and -insensitive pathways. Unlike iloprost, the stable prostacyclin analogue cicaprost (ZK 96480), is devoid of agonistic properties at prostaglandin E2 receptors. We compared the effects of cicaprost, iloprost and PGE2 on [Ca2+]i in HEL cells. Cicaprost, iloprost and PGE2 were similarly potent to increase [Ca2+]i in HEL cells. However, unlike the effects of PGE2, those of the prostacyclin analogues were not inhibited by pertussis toxin. The prostaglandins studied increased [Ca2+]i through both mobilization from internal stores and Ca2+ influx from the extracellular space. Prostacyclin analogue- and PGE2-induced rises in [Ca2+]i were desensitized in a homologous manner. Additionally, there was cross-desensitization between cicaprost and iloprost, but not between the prostacyclin analogues and PGE2. Our data suggest that in HEL cells (i) cicaprost and iloprost act through prostacyclin receptors and (ii) that these receptors couple to pertussis toxin-insensitive heterotrimeric regulatory guanine nucleotide-binding proteins, (iii) resulting in an increase in [Ca2+]i by Ca2+ mobilization from internal stores and sustained influx.</p>","PeriodicalId":11520,"journal":{"name":"Eicosanoids","volume":"5 Suppl ","pages":"S10-2"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12455502","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}
{"title":"Regulation of leukotriene biosynthesis in human polymorphonuclear leukocytes.","authors":"M Schatz-Munding, V Ullrich","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Since the formation of leukotrienes in human polymorphonuclear leukocytes is Ca-dependent we have determined the Ca-pools involved and the enzymes affected. With PAF, fMLP and LTB4 as agonists the Ca-transients measured with Fura-2 showed the same height of the intracellular Ca-signal but an external Ca-component in decreasing magnitude. In parallel the activity of 5-lipoxygenase was also decreasing. 5-lipoxygenase was linearly dependent on Ca with saturation of around 350 nMol/l already provided by the release of intracellular Ca. Phospholipase A2, however, started to activate at about this concentration. Hence arachidonate is a limiting factor in stimulated leukocytes due to a limited influx of extracellular Ca.</p>","PeriodicalId":11520,"journal":{"name":"Eicosanoids","volume":"5 Suppl ","pages":"S35-6"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12507506","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}
{"title":"Formation of lipoxins and leukotrienes by human alveolar macrophages incubated with 15(S)-HETE: a model for cellular cooperation between macrophages and airway epithelial cells.","authors":"C Chavis, P Godard, A Crastes de Paulet, M Damon","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Human alveolar macrophages (AM) from bronchoalveolar lavage of asthmatic patients (AP) and healthy volunteers (HS) were compared for their respective capacities to produce lipoxins and leukotrienes when stimulated by calcium ionophore A23187 with or without 15(S)-HETE. The metabolites were analyzed using an isocratic RP-HPLC system and their formation profiles evaluated on the basis of chromatographic behaviour, UV spectral characteristics and co-elution with synthetic standards. Without 15-HETE, AM from AP produced more LTB4 and 5-HETE than those from HS. In the presence of 15-HETE, human AM were able to produce 5,15-diHETE and lipoxins. Moreover, the total amount of lipoxins synthesized by AM from AP was 2 fold higher than that synthesized by AM from HS, thus showing an enhanced cell activation via the 5-lipoxygenase (5-LO) pathway. These results presented AM as in vitro 15-HETE metabolizing cells and suggested some hypothesis about human AM 5-LO regulation mechanism. The enhanced 5-LO activity in AM from AP suggested that in vivo they could participate in cell to cell interaction mechanisms involved in inflammatory lung diseases and might also take up and transform 15-HETE predominantly released by airway epithelial cells.</p>","PeriodicalId":11520,"journal":{"name":"Eicosanoids","volume":"5 3-4","pages":"203-11"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12511419","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}
M Toppozada, F Gerges, H Khalil, S Marzouk, A Kholeif
{"title":"Effect of prostaglandin E2 or prostaglandin synthesis inhibitors on human gonadotrophins and prolactin.","authors":"M Toppozada, F Gerges, H Khalil, S Marzouk, A Kholeif","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>A role for prostaglandins (PGs) in the release of pituitary hormones in humans is controversial. The effect of PGE2 or PG synthesis inhibitors on gonadotrophin and prolactin (PRL) levels was evaluated in 50 volunteers (25 males and 25 females). Forty cases in four equal groups (Group I & II were males and group III & IV were females) received iv infusion of PGE2 in one cycle and non-steroidal anti-inflammatory drugs (NSAID) [Indomethacin or Naproxen] in the subsequent cycle. Control groups A & B (5 males and 5 females) received saline infusions in one cycle and placebo capsules in the next cycle. Neither PGE2 nor any of the two NSAID altered the basal levels of FSH or LH significantly. PGE2 infusions in males depressed PRL levels significantly two hours after the onset of infusions. Indomethacin raised PRL levels while Naproxen did not. In women, a similar response was also observed but prolactin levels decreased earlier (30 min from the PGE2 infusion). These data indicate a probable role for PGE2 or other prostanoids as well in the regulation of human PRL release but not in gonadotrophin secretion.</p>","PeriodicalId":11520,"journal":{"name":"Eicosanoids","volume":"5 1","pages":"23-7"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12589783","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}
M Bachelet, C Chouaid, N Havet, J Masliah, A Barre, B Housset, B B Vargaftig
{"title":"Modulation of arachidonic acid metabolism and cyclic AMP content of human alveolar macrophages.","authors":"M Bachelet, C Chouaid, N Havet, J Masliah, A Barre, B Housset, B B Vargaftig","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The exposure of human alveolar macrophages to inflammatory mediators such as PAF (1 microM), fMLP (1 microM) or the calcium ionophore A23187 (1 microM) induced a rapid decrease in their intracellular concentration of cAMP. Inhibition of TXA2 synthesis by the specific thromboxane synthase inhibitor ridogrel (1-10 microM) or by non-specific inhibitors as indomethacin (1-10 microM), the cyclooxygenase inhibitor, or BW A4C (1-10 microM), the 5-lipoxygenase inhibitor, partially prevented the decrease in cAMP induced by the different inflammatory stimuli. Evidence for an indirect control of cAMP levels in human alveolar macrophages by inflammatory mediators through the production of arachidonic acid derivatives from the cyclooxygenase pathway is supported by this study.</p>","PeriodicalId":11520,"journal":{"name":"Eicosanoids","volume":"5 3-4","pages":"185-90"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12511418","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}
G E Rice, S P Brennecke, K F Scott, G M Smith, I A Rajkovic, G J Bishop
{"title":"Elevated maternal plasma immunoreactive phospholipase A2 in human preterm and term labour.","authors":"G E Rice, S P Brennecke, K F Scott, G M Smith, I A Rajkovic, G J Bishop","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Peripheral plasma concentrations of immunoreactive phospholipase A2 (irPLA2) (Type II, non-pancreatic) were determined in 110 women during pregnancy. The concentration of irPLA2 did not significantly change during pregnancy (5.7 +/- 0.6 ng/ml, n = 72) until the onset of labour. When compared with non-labouring women, irPLA2 concentrations were significantly elevated in association with both preterm labour (13.3 +/- 2.4 ng/ml, n = 15, p less than 0.02) and labour at term (10.4 +/- 1.7, n = 23, p less than 0.02). These data suggest that maternal plasma irPLA2 may be reflective of the mechanism(s) underlying the labour-associated increase in human gestational tissue eicosanoid formation.</p>","PeriodicalId":11520,"journal":{"name":"Eicosanoids","volume":"5 1","pages":"9-12"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12590463","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}
H Sinzinger, I Virgolini, J O'Grady, A Keiler, G Lupattelli, P Angelberger, E Molinari
{"title":"Aspirin abolishes the decreased low-density lipoprotein (LDL) entry into the rabbit arterial wall induced by the calcium channel blocker isradipine.","authors":"H Sinzinger, I Virgolini, J O'Grady, A Keiler, G Lupattelli, P Angelberger, E Molinari","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>After deendothelialization and experimentally induced hypercholesterolemia in rabbits, an increased LDL entry into the vascular wall can be monitored using radiolabelled LDL. In male rabbits aged 6 months the abdominal aortic endothelium was removed by a Fogarty catheter. The animals fed a 1% cholesterol supplemented diet were treated either with isradipine (0.3 mg/kg/daily) (n = 36) alone or in combination with aspirin (5 mg/kg/daily) (n = 36) for four weeks. Thirty-six animals served as controls. 1, 3, 6, 12, 24 and 48 hours prior to sacrificing, 10 microCi 125I-LDL was administered intravenously to six rabbits in each group. The LDL entry was quantified in the abdominal aorta according to morphologically assessed type of surface lining. Aortic cholesterol content was assessed by Sudan-III staining and quantitative determination. Endothelialized segments exhibited a significantly (p less than 0.05 - p less than 0.001) lower LDL uptake as compared to re- or deendothelialized segments. The LDL entry was significantly lower with isradipine treatment than in controls. In parallel the cholesterol content decreased and the Sudan-III-positive areas were smaller in size. This beneficial effect as well as that on aortic lipid content was abolished by a pretreatment with aspirin. While in the isradipine-treated animals PGI2 synthesis was significantly (p less than 0.01) enhanced, it was almost completely blocked by aspirin. These findings indicate that the benefit of reduced LDL entry caused by isradipine may be mediated by an increased endogenous PGI2 synthesis.</p>","PeriodicalId":11520,"journal":{"name":"Eicosanoids","volume":"5 1","pages":"13-6"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12589781","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}
{"title":"Lipoxygenase inhibitors but not site specific 5-lipoxygenase blockers protect against endotoxic shock and inhibit production of tumor necrosis factor.","authors":"F U Schade, R Engel, D Jakobs","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In the present study it was found that lipoxygenase inhibitors prevent LPS-, but not tumor necrosis factor alpha (TNF alpha)-evoked lethality. The specific 5-lipoxygenase inhibitors (MK-886, CGS-8515) were uneffective in endotoxin-induced shock. The 5-lipoxygenase inhibitors interfered with LTC4 formation in macrophages while they did not affect endotoxin induced TNF alpha-formation, neither in cell cultures nor in mice. The potency of other, less specific lipoxygenase blockers to suppress TNF alpha formation correlated quantitatively with their ability to interfere with 13-HODD synthesis. Based on the fact that a tight correlation exists between inhibition of TNF alpha synthesis and 13-HODD formation, this product might be important for TNF alpha formation.</p>","PeriodicalId":11520,"journal":{"name":"Eicosanoids","volume":"5 Suppl ","pages":"S45-7"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12620247","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}
{"title":"Epidermal derived growth factor stimulates the prostaglandin F2 alpha-synthesis in rabbit luteal cells.","authors":"C Chudaska, R Diallo, W Schlegel","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Isolated rabbit luteal cells from day 6 and 12 of pseudopregnancy were cultured with hCG, EGF, and EGF together with arachidonic acid (AA) in serum-free culture medium for 96 hours. The hCG stimulation of the progesterone (P) synthesis was more pronounced on day 6 then on day 12. EGF alone did not change significantly the production of either P or PGF2 alpha. AA increased the production of PGF2 alpha on day 6 and 12 significantly (3.9-fold on day 6, P < 0.005; 7-fold on day 12, P < 0.001). AA together with EGF increased the level of PGF2 alpha more pronounced when compared with AA alone (7.2-fold on day 6, P < 0.025; 9.8-fold on day 12, P < 0.05). The progesterone production of the cells remained unchanged during EGF exposure. We conclude that EGF together with AA is able to stimulate the PGF2 alpha biosynthesis in cultured rabbit luteal cells. Therefore, EGF could be relevant as an additional regression factor in rabbits. This mechanism seems to be independent from the progesterone synthesis.</p>","PeriodicalId":11520,"journal":{"name":"Eicosanoids","volume":"5 Suppl ","pages":"S48-50"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12620248","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}
{"title":"Membranes exert indirect negative control on phospholipase A2 (PLA2) in human placenta.","authors":"J Y Jeremy, M A Barradas, D P Mikhailidis","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":11520,"journal":{"name":"Eicosanoids","volume":"5 1","pages":"57-8"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12590462","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}