{"title":"Prostaglandin E2 stimulates sodium reabsorption in MDCK C7 cells, a renal collecting duct principal cell model.","authors":"M Wegmann, R M Nüsing","doi":"10.1016/j.plefa.2003.06.002","DOIUrl":"https://doi.org/10.1016/j.plefa.2003.06.002","url":null,"abstract":"<p><p>We examined the direct epithelial effects of the major product of arachidonic acid metabolism in the kidney, prostaglandin E(2) (PGE(2)), on ion transport and signal transduction in the hormone-sensitive Madin-Darby canine kidney (MDCK) C7 subclone as a model of renal collecting duct principal cells. MDCK C7 cells were grown on microporous permeable filter supports and mounted in Ussing-type chambers. Reverse transcriptase (RT)-PCR and sequencing were used to determine E-prostanoid (EP) receptor expression. Basolateral and, about 14-fold less potent, apical addition of PGE(2) increased short-circuit current (I(sc)) in a concentration-dependent manner. This ion transport was biphasic with a rapid peak not detectable under chloride-free conditions. The remaining, stably elevated current was unaffected by furosemide, hydrochlorothiazide, ethylisopropanol amiloride, and 5-nitro-2-(3-phenyl-propyl-amino)benzoic acid (NPPB). In contrast, apical amiloride (10 microM) significantly decreased I(sc), indicating sodium reabsorption. The effect of PGE(2) was attenuated in the presence of vasopressin. Agonists acting by cAMP elevation like dibutyryl-cAMP and theophylline also induced an amiloride-sensitive ion transport with similar kinetics as PGE(2). Moreover, PGE(2) rapidly increased intracellular cAMP levels. RT-PCR demonstrated mRNA expression of the epithelial sodium channel (ENaC), and of the EP2 receptor in MDCK C7 cells. Accordingly, EP2 receptor agonist butaprost mimicked PGE(2) epithelial action. In conclusion, PGE(2) induces amiloride-sensitive sodium reabsorption in MDCK C7 monolayers. This ion transport is most likely mediated by EP2 receptor activation leading to increased intracellular cAMP levels. Therefore, PGE(2) might also contribute to Na(+) reabsorption in the mammalian collecting duct.</p>","PeriodicalId":20659,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2003-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.plefa.2003.06.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24046553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cyclooxygenase 2 (COX2)-prostanoid pathway and liver diseases.","authors":"Ke-Qin Hu","doi":"10.1016/j.plefa.2003.07.001","DOIUrl":"https://doi.org/10.1016/j.plefa.2003.07.001","url":null,"abstract":"<p><p>Cycloocygenases 2 (COX2)-prostanoid pathway plays important and complex roles in the pathogenesis of various liver diseases. Most studies indicated that COX2-prostanoid pathway might suppress hepatic fibrogenesis by decreasing proliferation, migration, and contractility of hepatic stellate cells (HSCs). In animal model, COX2-prostanoid pathway increases portal hypertension, which can be reduced by treatment with COX2 inhibitor. In cirrhosis, COX2-prostanoid pathway may reduce formation of ascites by enhancing free water excretion, and protect gastric mucosa from ulcerative insults. Aberrant expression of COX2 has been well associated with hepatocarcinogenesis. COX2 inhibitors can effectively suppress proliferation of hepatocellular carcinoma (HCC) cells. This provided rationale for further testing COX2 inhibitors as clinical agents for HCC chemoprovention. Further studies will be needed to examine how COX2 inhibitors affect pathogenesis of various liver diseases.</p>","PeriodicalId":20659,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2003-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.plefa.2003.07.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24046555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Regulation of the human thromboxane A2 receptor gene in human megakaryoblastic MEG-01 cells.","authors":"T Saffak, S Schäfer, C Haas, R M Nüsing","doi":"10.1016/s0952-3278(03)00112-1","DOIUrl":"https://doi.org/10.1016/s0952-3278(03)00112-1","url":null,"abstract":"<p><p>Thromboxane A(2) (TXA(2)) is an important mediator for platelet aggregation and blood vessel constriction. TXA(2) receptor (TP receptor) is expressed in different cell types including smooth muscle cells, endothelial cells and platelets. Expression level of TP receptor may modulate the action of TXA(2) on target cells. In megakaryoblastic MEG-01 cells, a cell line representing a model for platelet precursor cells, addition of phorbolester 12-O-tetradecanoylphorbol-13-acetate (TPA) caused an increase in transcriptional activity of TP receptor gene promoter. Within 20 h a rise in expression of TP receptor mRNA and protein was observed. The effect of TPA was concentration-dependent and was blocked by specific inhibitors of protein kinase C. Flow cytometry analysis indicated that the increase in TP receptor expression appeared to be one of the earliest events in the course of TPA-induced maturation of MEG-01 cells. Stimulation of the protein kinase A pathway by incubation with forskolin or IBMX caused a decrease in transcriptional activity. Promoter deletion experiments indicated that the responsive elements for protein kinase A and C are located upstream and downstream, respectively, of -700 bp of the TP receptor gene. These experiments indicate that the expression of the human thromboxane receptor is differently regulated in platelet precursor cells by the protein kinase A and C pathway.</p>","PeriodicalId":20659,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2003-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/s0952-3278(03)00112-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24046550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M J Bellini, M P Polo, M J T de Alaniz, M G de Bravo
{"title":"Effect of simvastatin on the uptake and metabolic conversion of palmitic, dihomo-gamma-linoleic and alpha-linolenic acids in A549 cells.","authors":"M J Bellini, M P Polo, M J T de Alaniz, M G de Bravo","doi":"10.1016/s0952-3278(03)00149-2","DOIUrl":"https://doi.org/10.1016/s0952-3278(03)00149-2","url":null,"abstract":"<p><p>It is well known that simvastatin affects cholesterol synthesis. Furthermore it inhibits growth and proliferation and perturbs fatty acid metabolism in some cell lines. We have studied the effects of simvastatin on the uptake and metabolism of exogenous fatty acid in the human lung adenocarcinoma A549 cells. Simvastatin inhibited the proliferation of A549, and caused an increment in phospholipid/cholesterol ratio due to an increment in phospholipid content without affecting cholesterol content. All the fatty acids were uptaken and metabolized in both control and treated cells. The conversion of palmitic, linoleic and dihomo-gamma-linoleic acids to their metabolites and products/precursor ratios for the desaturation and elongation reactions showed that simvastatin enhanced the Delta5 desaturation step and altered some elongating steps. The machinery for unsaturated fatty acid synthesis in A549 is quite sensitive to simvastatin and its effects could have important implication taking into account that highly unsaturated fatty acids are involved in the regulation of diverse cellular functions by themselves or through their metabolites.</p>","PeriodicalId":20659,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2003-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/s0952-3278(03)00149-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24045985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tadaatsu Imaizumi, Mika Kumagai, Masaharu Hatakeyama, Wakako Tamo, Koji Yamashita, Hidemi Yoshida, Hirofumi Munakata, Kei Satoh
{"title":"Effect of 15-deoxy-delta12,14-prostaglandin J2 on IL-1beta-induced expression of epithelial neutrophil-activating protein-78 in human endothelial cells.","authors":"Tadaatsu Imaizumi, Mika Kumagai, Masaharu Hatakeyama, Wakako Tamo, Koji Yamashita, Hidemi Yoshida, Hirofumi Munakata, Kei Satoh","doi":"10.1016/s0952-3278(03)00145-5","DOIUrl":"https://doi.org/10.1016/s0952-3278(03)00145-5","url":null,"abstract":"<p><p>Epithelial neutrophil-activating peptide-78 (ENA-78) is a member of CXC chemokines. It is produced by endothelial cells stimulated with interleukin-1 (IL-1), along with other CXC chemokines such as IL-8 and growth-related oncogene protein-alpha (GRO-alpha). IL-1-induced ENA-78 production by endothelial cells may be important for the regulation of neutrophil activation. 15-Deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) is a natural ligand for peroxisome proliferator-activated receptor-gamma (PPAR-gamma) and affects the expression of various genes. We examined the effect of 15d-PGJ(2) on the expression of ENA-78 in cultured endothelial cells stimulated with IL-1beta. 15d-PGJ(2) inhibited the IL-1beta-induced expression of ENA-78, but not the expression of IL-8 or GRO-alpha in response to IL-1. Ciglitazone, another agonist for PPAR-gamma, had no effect on the expression of ENA-78, suggesting that 15d-PGJ(2) may inhibit the expression of ENA-78 in a PPAR-gamma-independent manner. 15d-PGJ(2) may modulate inflammatory reactions by regulating the balance of CXC chemokines in endothelial cells.</p>","PeriodicalId":20659,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2003-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/s0952-3278(03)00145-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24046554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jan M Schwab, Hermann J Schluesener, Richard Meyermann, Charles N Serhan
{"title":"COX-3 the enzyme and the concept: steps towards highly specialized pathways and precision therapeutics?","authors":"Jan M Schwab, Hermann J Schluesener, Richard Meyermann, Charles N Serhan","doi":"10.1016/j.plefa.2003.07.003","DOIUrl":"https://doi.org/10.1016/j.plefa.2003.07.003","url":null,"abstract":"<p><p>Cyclooxygenases (COXs) catalyse the key rate-limiting step in prostanoid and thromboxane biosynthesis and are targets of non-steroidal anti-inflammatory drugs (NSAIDs). Until recently, the presence of only two isoforms-COX-1 and COX-2-remained in question because the potent anti-pyretic and analgesic effects of acetaminophen (paracetamol, tylenol ben-u-ron) could not be explained by either COX-1 or COX-2 blockades. A novel COX-1 splice variant termed COX-3, sensitive to acetaminophen, was recently discovered by Simmons et al., and is considered to play a key role in the biosynthesis of prostanoids known to be important mediators in pain and fever. Drugs that preferential block COX-1 also appear to act at COX-3. However the existence of COX-3 at the nucleotide sequence level in humans has been called to question. A functional COX-3 in humans is still to come underlining that the concept of COX-3 is still attractive. Here, we discuss some of the implications drawn from the identification of additional functional cyclooxygenase members in the generation of bioactive autacoids.</p>","PeriodicalId":20659,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2003-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.plefa.2003.07.003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24046556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
T Tognetti, A Estevez, C G Luchetti, V Sander, A M Franchi, A B Motta
{"title":"Relationship between endothelin 1 and nitric oxide system in the corpus luteum regression.","authors":"T Tognetti, A Estevez, C G Luchetti, V Sander, A M Franchi, A B Motta","doi":"10.1016/j.plefa.2003.07.002","DOIUrl":"https://doi.org/10.1016/j.plefa.2003.07.002","url":null,"abstract":"<p><p>The present study was designed to investigate the relationship between the nitric oxide (NO) system and endothelin 1 (ET-1) in the mechanism of corpus luteum (CL) development and consequently regression in rats. We first evaluated basal ET-1 levels in ovarian tissue from rats with different stages of CL development. An increased ovarian ET-1 content was found during CL regression. In a dose-department response, ET-1 decreased progesterone (P4) and increased prostaglandin (PG) PGF2alpha production. By means of a competitive nitric oxide synthase (NOS) inhibitor: L-nitro arginine methyl ester (L-NAME) and a slow NO releasing: diethyl-aminetriamine (DETA-NONOate), we demonstrated that NO system could be the intermediary in the ET-1 diminishing P4 production. The Western blot analysis revealed an increase on iNOS while eNOS protein expression was diminished. We also found a diminution of total NOS activity after ET-1 treatment. These data suggest the existence of a functional relationship between ET-1 and NOS isoforms leading the regulation of CL functionally.</p>","PeriodicalId":20659,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2003-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.plefa.2003.07.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24045986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Helen Fox, Brian M Ross, Douglas Tocher, David Horrobin, Iain Glen, David St Clair
{"title":"Degradation of specific polyunsaturated fatty acids in red blood cells stored at -20 degrees C proceeds faster in patients with schizophrenia when compared with healthy controls.","authors":"Helen Fox, Brian M Ross, Douglas Tocher, David Horrobin, Iain Glen, David St Clair","doi":"10.1016/s0952-3278(03)00084-x","DOIUrl":"https://doi.org/10.1016/s0952-3278(03)00084-x","url":null,"abstract":"<p><p>Deficits in red blood cell (RBC) polyunsaturated fatty acids (PUFAs) have been extensively reported in schizophrenia although reports are inconsistent. A possible explanation for this inconsistency is varying storage conditions of blood samples prior to analysis, especially freezer storage temperature. We conducted a prospective investigation of fatty acid degradation rates in RBCs from healthy control subjects when samples from each individual were stored at both -20 degrees C or -70 degrees C. Differences were detected between storage conditions. A second prospective study was conducted to investigate the effect of differential storage conditions on RBC membrane fatty acids from schizophrenic patients. We found that storage at -20 degrees C was associated with reduced levels of PUFAs. Comparison of decay rates suggest that schizophrenics decay approximately twice as rapidly as controls. Furthermore, this phenomenon appears to be specific for the longer chain PUFAs suggesting that an enzymatic process may be responsible, e.g. elevated phospholipase A(2) activity, as opposed to simple chemical oxidation.</p>","PeriodicalId":20659,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2003-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/s0952-3278(03)00084-x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24046551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Andreas Leonhardt, Alexander Glaser, Markus Wegmann, Reinhard Hackenberg, Rolf M Nüsing
{"title":"Expression of prostanoid receptors in human lower segment pregnant myometrium.","authors":"Andreas Leonhardt, Alexander Glaser, Markus Wegmann, Reinhard Hackenberg, Rolf M Nüsing","doi":"10.1016/s0952-3278(03)00113-3","DOIUrl":"https://doi.org/10.1016/s0952-3278(03)00113-3","url":null,"abstract":"<p><p>Prostanoids, especially prostaglandin (PG) E(2), are important mediators of uterine relaxation and contractions during gestation and parturition. Inhibitors of PG formation as well as PG analogues are used to modulate uterine tonus. So far, only limited data are available regarding the expression of prostanoid receptors in human pregnant myometrium. In the present study, the expression of the receptors for PGE(2) (EP1, EP2, EP3, EP4), PGF(2alpha) (FP), prostacyclin (IP), and thromboxane A(2) (TP) in human pregnant myometrium was studied by RT-PCR, in situ hybridization and immunohistochemistry. Myometrial tissue was obtained from five women at term and not in labour and from two women who delivered preterm. Tissue specimens were excised from the upper edge of the transverse lower uterine segment incision. In all tissues analysed, EP1, EP2, EP3, EP4, FP, TP and IP receptor mRNA and protein was detected. mRNA expression for PGD(2) (DP) receptor was not detected in the majority of tissue specimens. EP1, EP2, EP4, IP, TP and FP receptor protein was detected on myometrial smooth muscle cells, whereas EP3 receptor protein was only expressed by stromal and endothelial cells. In situ hybridization experiments yielded similar results. The expression of the EP2 receptor mRNA was inversely related to gestational age. We suggest that the contractile effect of PGE(2) at term is probably mediated directly by the EP1 receptor expressed in myometrial smooth muscle cells and indirectly by the EP3 receptor expressed in stromal cells and a decrease in EP2 receptor expression.</p>","PeriodicalId":20659,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2003-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/s0952-3278(03)00113-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24046552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Juha Alanko, Pasi Jolma, Peeter Kööbi, Asko Riutta, Jarkko Kalliovalkama, Jari Petteri Tolvanen, Ilkka Pörsti
{"title":"Prostacyclin and thromboxane A2 production in nitric oxide-deficient hypertension in vivo. Effects of high calcium diet and angiotensin receptor blockade.","authors":"Juha Alanko, Pasi Jolma, Peeter Kööbi, Asko Riutta, Jarkko Kalliovalkama, Jari Petteri Tolvanen, Ilkka Pörsti","doi":"10.1016/s0952-3278(03)00148-0","DOIUrl":"https://doi.org/10.1016/s0952-3278(03)00148-0","url":null,"abstract":"<p><p>The effects of chronic nitric oxide deficiency on prostacyclin and thromboxane A(2) production in vivo are unknown. Therefore, we treated rats with N(G)-nitro-L-arginine methyl ester (L-NAME), and used losartan and high calcium diet as antihypertensive treatments. Forty eight Wistar rats were divided into six groups: control; losartan (20mgkg(-1)day(-1)); high calcium diet (dietary calcium elevated from 1.1% to 3%); L-NAME (20mgkg(-1)day(-1)); losartan+L-NAME and high calcium diet+L-NAME. Prostacyclin and thromboxane A(2) production were measured after eight weeks as urinary 2,3-dinor-6-keto-PGF(1alpha) and 11-dehydro-TXB(2), respectively. Both the high calcium diet and losartan reduced blood pressure in L-NAME hypertension. Chronic nitric oxide deficiency did not modulate prostacyclin production but it nearly doubled thromboxane A(2) production in vivo. This effect was not influenced by lowering of blood pressure by blockade of angiotensin II type 1 receptors. Independent of the level of blood pressure and blockade of nitric oxide synthesis the high calcium diet decreased prostacyclin production by one third and increased thromboxane A(2) production almost two-fold in vivo.</p>","PeriodicalId":20659,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2003-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/s0952-3278(03)00148-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24046557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}