Quantitative metabolic profiling of lipid mediators.

Lipids are heterogeneous biological molecules that possess multiple physiological roles including cell structure, homeostasis, and restoration of tissue functionality during and after inflammation. Lipid metabolism constitutes a network of pathways that are related at multiple biosynthetic hubs. Disregulation of lipid metabolism can lead to pathophysiological effects and multiple lipid mediators have been described to be involved in physiological processes, (e.g. inflammation). Accordingly, a thorough description of these pathways may shed light on putative relations in multiple complex diseases, including chronic obstructive pulmonary disease, asthma, Alzheimer's disease, multiple sclerosis, obesity, and cancer. Due to the structural complexity of lipids and the low abundance of many lipid mediators, mass spectrometry is the most commonly employed method for analysis. However, multiple challenges remain in the efforts to analyze every lipid subfamily. In this review, the biological role of sphingolipids, glycerolipids, oxylipins (e.g. eicosanoids), endocannabinoids, and N-acylethanolamines in relation to health and disease and the state-of-the-art analyses are summarized. The characterization and understanding of these pathways will increase our ability to examine for interrelations among lipid pathways and improve the knowledge of biological mechanisms in health and disease.

[1]  S. Dahlén,et al.  Quantification of lipid mediator metabolites in human urine from asthma patients by electrospray ionization mass spectrometry: controlling matrix effects. , 2013, Analytical chemistry.

[2]  R. Mayer,et al.  In vitro and in vivo characterization of a novel soluble epoxide hydrolase inhibitor. , 2013, Prostaglandins & other lipid mediators.

[3]  Dolores Corella,et al.  Primary prevention of cardiovascular disease with a Mediterranean diet. , 2013, The New England journal of medicine.

[4]  G. Nilsson,et al.  Lipid mediator metabolic profiling demonstrates differences in eicosanoid patterns in two phenotypically distinct mast cell populations[S] , 2013, Journal of Lipid Research.

[5]  A. Dannenberg,et al.  Sphingolipid signaling in metabolic disorders. , 2012, Cell metabolism.

[6]  J. Walter,et al.  Sphingolipids: critical players in Alzheimer's disease. , 2012, Progress in lipid research.

[7]  Hua Dong Metabolomic Profiling of Lipids for Biomarker Discovery , 2012 .

[8]  D. Yao,et al.  Effect of Prostaglandin E1 on Pulmonary Arterial Hypertension Following Corrective Surgery for Congenital Heart Disease , 2012, Journal of cardiovascular pharmacology and therapeutics.

[9]  M. Spite,et al.  Resolvins: anti-inflammatory and proresolving mediators derived from omega-3 polyunsaturated fatty acids. , 2012, Annual review of nutrition.

[10]  A. Clark,et al.  The potential role of sphingolipid-mediated cell signaling in the interaction between hyperglycemia, acute myocardial infarction and heart failure , 2012, Expert opinion on therapeutic targets.

[11]  S. Bijlsma,et al.  Time-dependent effect of in vivo inflammation on eicosanoid and endocannabinoid levels in plasma, liver, ileum and adipose tissue in C57BL/6 mice fed a fish-oil diet. , 2012, International immunopharmacology.

[12]  S. Grinstein,et al.  Phosphatidylserine dynamics in cellular membranes , 2012, Molecular biology of the cell.

[13]  E. Hogan,et al.  Signaling and Regulatory Functions of Bioactive Sphingolipids as Therapeutic Targets in Multiple Sclerosis , 2012, Neurochemical Research.

[14]  J. Haeggström,et al.  Allergic Asthmatics Show Divergent Lipid Mediator Profiles from Healthy Controls Both at Baseline and following Birch Pollen Provocation , 2012, PloS one.

[15]  D. Tsikas,et al.  Simultaneous UPLC-MS/MS quantification of the endocannabinoids 2-arachidonoyl glycerol (2AG), 1-arachidonoyl glycerol (1AG), and anandamide in human plasma: minimization of matrix-effects, 2AG/1AG isomerization and degradation by toluene solvent extraction. , 2012, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[16]  D. Hafler,et al.  Fingolimod for multiple sclerosis. , 2012, The New England journal of medicine.

[17]  Ananda Sen,et al.  Effect of Fish Oil on Levels of R- and S-Enantiomers of 5-, 12-, and 15-Hydroxyeicosatetraenoic Acids in Mouse Colonic Mucosa , 2012, Nutrition and cancer.

[18]  H. Kinney,et al.  Aberrant Upregulation of Astroglial Ceramide Potentiates Oligodendrocyte Injury , 2012, Brain pathology.

[19]  Y. Liu,et al.  Analysis of mammalian sphingolipids by liquid chromatography tandem mass spectrometry (LC-MS/MS) and tissue imaging mass spectrometry (TIMS). , 2011, Biochimica et biophysica acta.

[20]  D. Tsikas,et al.  Quantification of endocannabinoids in biological systems by chromatography and mass spectrometry: a comprehensive review from an analytical and biological perspective. , 2011, Biochimica et biophysica acta.

[21]  K. Sandhoff,et al.  Mass spectrometric analysis of neutral sphingolipids: methods, applications, and limitations. , 2011, Biochimica et biophysica acta.

[22]  L. Marnett,et al.  Cannabinoids, endocannabinoids, and cancer , 2011, Cancer and Metastasis Reviews.

[23]  C. Rao,et al.  Role of lipoxins, resolvins, and other bioactive lipids in colon and pancreatic cancer , 2011, Cancer and Metastasis Reviews.

[24]  C. Serhan,et al.  Resolvins and protectins in inflammation resolution. , 2011, Chemical reviews.

[25]  Alfred H. Merrill,et al.  Sphingolipid and Glycosphingolipid Metabolic Pathways in the Era of Sphingolipidomics , 2011, Chemical reviews.

[26]  J. Haeggström,et al.  Lipoxygenase and leukotriene pathways: biochemistry, biology, and roles in disease. , 2011, Chemical reviews.

[27]  N. Krug,et al.  Allergen Challenge Increases Anandamide in Bronchoalveolar Fluid of Patients With Allergic Asthma , 2011, Clinical pharmacology and therapeutics.

[28]  Anders Eklund,et al.  Asthmatics Exhibit Altered Oxylipin Profiles Compared to Healthy Individuals after Subway Air Exposure , 2011, PloS one.

[29]  P. Axelsen,et al.  Mass spectrometric analysis of long-chain lipids. , 2011, Mass spectrometry reviews.

[30]  S. Dahlén,et al.  Lipid mediator profiling in pulmonary disease. , 2011, Current pharmaceutical biotechnology.

[31]  Garret A. FitzGerald,et al.  Prostaglandins and Inflammation , 2011, Arteriosclerosis, thrombosis, and vascular biology.

[32]  B. Hammock,et al.  Soluble epoxide hydrolase in the generation and maintenance of high blood pressure in spontaneously hypertensive rats. , 2011, American journal of physiology. Endocrinology and metabolism.

[33]  S. Tangye,et al.  Inflammatory Mechanisms in Obesity , 2013 .

[34]  Mengtao Zhou,et al.  The protective effects of Lipoxin A4 during the early phase of severe acute pancreatitis in rats , 2011, Scandinavian journal of gastroenterology.

[35]  T. Uyama,et al.  Enzymological studies on the biosynthesis of N-acylethanolamines. , 2010, Biochimica et biophysica acta.

[36]  M. Mielke,et al.  Disturbance in cerebral spinal fluid sphingolipid content is associated with memory impairment in subjects infected with the human immunodeficiency virus , 2010, Journal of NeuroVirology.

[37]  Valerie B. O’Donnell,et al.  Molecular enzymology of lipoxygenases. , 2010, Archives of biochemistry and biophysics.

[38]  Eoin Fahy,et al.  Lipidomics reveals a remarkable diversity of lipids in human plasma1[S] , 2010, Journal of Lipid Research.

[39]  Christian Skonberg,et al.  Pitfalls in the sample preparation and analysis of N-acylethanolamines[S] , 2010, Journal of Lipid Research.

[40]  T. Uyama,et al.  N-acylethanolamine metabolism with special reference to N-acylethanolamine-hydrolyzing acid amidase (NAAA). , 2010, Progress in lipid research.

[41]  C. Serhan Novel lipid mediators and resolution mechanisms in acute inflammation: to resolve or not? , 2010, The American journal of pathology.

[42]  Michael I. Miller,et al.  Plasma ceramides are altered in mild cognitive impairment and predict cognitive decline and hippocampal volume loss , 2010, Alzheimer's & Dementia.

[43]  Hongbo Chi,et al.  S1P1-mTOR axis directs the reciprocal differentiation of TH1 and regulatory T cells , 2010, Nature Immunology.

[44]  N. Haughey Sphingolipids in Neurodegeneration , 2010, NeuroMolecular Medicine.

[45]  L. Kappos,et al.  Th17 central memory T cells are reduced by FTY720 in patients with multiple sclerosis , 2010, Neurology.

[46]  W. Harris,et al.  Detection of omega-3 oxylipins in human plasma and response to treatment with omega-3 acid ethyl esters[S] , 2010, Journal of Lipid Research.

[47]  K. Pahan,et al.  Sphingolipids in Multiple Sclerosis , 2010, NeuroMolecular Medicine.

[48]  H. Fyrst,et al.  An update on sphingosine-1-phosphate and other sphingolipid mediators. , 2010, Nature chemical biology.

[49]  J. Balsinde,et al.  Lipidomic approaches to the study of phospholipase A2-regulated phospholipid fatty acid incorporation and remodeling. , 2010, Biochimie.

[50]  L. Parsons,et al.  Quantification of brain endocannabinoid levels: methods, interpretations and pitfalls , 2010, British journal of pharmacology.

[51]  S. Grinstein,et al.  The distribution and function of phosphatidylserine in cellular membranes. , 2010, Annual review of biophysics.

[52]  Charles N Serhan,et al.  Resolvins RvE1 and RvD1 attenuate inflammatory pain via central and peripheral actions , 2010, Nature Medicine.

[53]  J. Balsinde,et al.  Markers of Monocyte Activation Revealed by Lipidomic Profiling of Arachidonic Acid-Containing Phospholipids , 2010, The Journal of Immunology.

[54]  V. Natarajan,et al.  Neurons and Oligodendrocytes Recycle Sphingosine 1-Phosphate to Ceramide , 2010, The Journal of Biological Chemistry.

[55]  H. Hartung,et al.  Mechanism of Action of Oral Fingolimod (FTY720) in Multiple Sclerosis , 2010, Clinical neuropharmacology.

[56]  Xianlin Han,et al.  Absence of oligodendroglial glucosylceramide synthesis does not result in CNS myelin abnormalities or alter the dysmyelinating phenotype of CGT‐deficient mice , 2010, Glia.

[57]  William W. Busse,et al.  Asthma: Clinical expression and molecular mechanisms , 2010, Journal of Allergy and Clinical Immunology.

[58]  C. Lyketsos,et al.  Serum sphingomyelins and ceramides are early predictors of memory impairment , 2010, Neurobiology of Aging.

[59]  T. Grosser,et al.  Emotion recollected in tranquility: lessons learned from the COX-2 saga. , 2010, Annual review of medicine.

[60]  C. Tench,et al.  Plasma endocannabinoid levels in multiple sclerosis , 2009, Journal of the Neurological Sciences.

[61]  J. Balsinde,et al.  Control of free arachidonic acid levels by phospholipases A2 and lysophospholipid acyltransferases. , 2009, Biochimica et biophysica acta.

[62]  S. Paruchuri,et al.  Leukotriene E4–induced pulmonary inflammation is mediated by the P2Y12 receptor , 2009, The Journal of experimental medicine.

[63]  B. Levy,et al.  Resolvins and protectins: mediating solutions to inflammation , 2009, British journal of pharmacology.

[64]  Thomas Meitinger,et al.  Genetic Determinants of Circulating Sphingolipid Concentrations in European Populations , 2009, PLoS genetics.

[65]  R. Neubert,et al.  Normal phase liquid chromatography coupled to quadrupole time of flight atmospheric pressure chemical ionization mass spectrometry for separation, detection and mass spectrometric profiling of neutral sphingolipids and cholesterol. , 2009, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[66]  G. Nixon Sphingolipids in inflammation: pathological implications and potential therapeutic targets , 2009, British journal of pharmacology.

[67]  Jun Yang,et al.  Quantitative profiling method for oxylipin metabolome by liquid chromatography electrospray ionization tandem mass spectrometry. , 2009, Analytical chemistry.

[68]  H. Hansen,et al.  N-acylethanolamines, anandamide and food intake. , 2009, Biochemical pharmacology.

[69]  V. Perry,et al.  Systemic inflammation and disease progression in Alzheimer disease , 2009, Neurology.

[70]  Jeremy C. Allegood,et al.  Quantitative analysis of sphingolipids for lipidomics using triple quadrupole and quadrupole linear ion trap mass spectrometers[S] , 2009, Journal of Lipid Research.

[71]  Ian A Blair,et al.  Targeted chiral lipidomics analysis of bioactive eicosanoid lipids in cellular systems. , 2009, BMB reports.

[72]  Y. Ilan,et al.  Glucocerebroside: an evolutionary advantage for patients with Gaucher disease and a new immunomodulatory agent , 2009, Immunology and cell biology.

[73]  K. Verhoeckx,et al.  Development and validation of a quantitative method for the determination of 12 endocannabinoids and related compounds in human plasma using liquid chromatography-tandem mass spectrometry. , 2009, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[74]  C. Liu,et al.  15-Lipoxygenase-1 induces expression and release of chemokines in cultured human lung epithelial cells. , 2009, American journal of physiology. Lung cellular and molecular physiology.

[75]  D. Stafforini,et al.  The emerging roles of PAF acetylhydrolase This work was supported by National Institutes of Health Grants HL44513, HL35828, and HL087018. Published, JLR Papers in Press, October 6, 2008. , 2009, Journal of Lipid Research.

[76]  J. Morrow,et al.  Levels of Prostaglandin E Metabolite and Leukotriene E4 Are Increased in the Urine of Smokers: Evidence that Celecoxib Shunts Arachidonic Acid into the 5-Lipoxygenase Pathway , 2009, Cancer Prevention Research.

[77]  Christer S. Ejsing,et al.  Global analysis of the yeast lipidome by quantitative shotgun mass spectrometry , 2009, Proceedings of the National Academy of Sciences.

[78]  L. Cowart,et al.  Sphingolipids: players in the pathology of metabolic disease , 2009, Trends in Endocrinology & Metabolism.

[79]  C. Serhan,et al.  Maresins: novel macrophage mediators with potent antiinflammatory and proresolving actions , 2009, The Journal of experimental medicine.

[80]  Takao Shimizu,et al.  Lipid mediators in health and disease: enzymes and receptors as therapeutic targets for the regulation of immunity and inflammation. , 2009, Annual review of pharmacology and toxicology.

[81]  E. Hogan,et al.  T-cells expressing natural killer (NK) receptors are altered in multiple sclerosis and responses to α-galactosylceramide are impaired , 2008, Journal of the Neurological Sciences.

[82]  J. Antel,et al.  Central nervous system-directed effects of FTY720 (fingolimod) , 2008, Journal of the Neurological Sciences.

[83]  L. Cantley,et al.  PI3K pathway alterations in cancer: variations on a theme , 2008, Oncogene.

[84]  B. Levy,et al.  Resolvin E1 regulates interleukin 23, interferon-γ and lipoxin A4 to promote the resolution of allergic airway inflammation , 2008, Nature Immunology.

[85]  U. Jahn,et al.  Beyond prostaglandins--chemistry and biology of cyclic oxygenated metabolites formed by free-radical pathways from polyunsaturated fatty acids. , 2008, Angewandte Chemie.

[86]  P. Allavena,et al.  Cancer-related inflammation , 2008, Nature.

[87]  I. Adcock,et al.  Multifaceted mechanisms in COPD: inflammation, immunity, and tissue repair and destruction , 2008, European Respiratory Journal.

[88]  Charles N. Serhan,et al.  Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators , 2008, Nature Reviews Immunology.

[89]  A. Shevchenko,et al.  Lipid extraction by methyl-tert-butyl ether for high-throughput lipidomics. , 2008, Journal of lipid research.

[90]  R. Schneiter,et al.  Lipid signalling in disease , 2008, Nature Reviews Molecular Cell Biology.

[91]  Matej Oresic,et al.  Informatics and computational strategies for the study of lipids. , 2008, Molecular bioSystems.

[92]  Tony Yeung,et al.  Membrane Phosphatidylserine Regulates Surface Charge and Protein Localization , 2008, Science.

[93]  B. Cravatt,et al.  A Comprehensive Profile of Brain Enzymes that Hydrolyze the Endocannabinoid 2‐Arachidonoylglycerol , 2007, Chemistry & biology.

[94]  B. Levy,et al.  Lipoxin A4 stable analogs reduce allergic airway responses via mechanisms distinct from CysLT1 receptor antagonism , 2007, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[95]  R. Capasso,et al.  Role and regulation of acylethanolamides in energy balance: focus on adipocytes and β‐cells , 2007 .

[96]  May D. Wang,et al.  (Glyco)sphingolipidology: an amazing challenge and opportunity for systems biology. , 2007, Trends in biochemical sciences.

[97]  É. Rousseau,et al.  Functional effects of 20-HETE on human bronchi: hyperpolarization and relaxation due to BKCa channel activation. , 2007, American journal of physiology. Lung cellular and molecular physiology.

[98]  R. Proia,et al.  Essential role of sphingosine 1-phosphate receptor 2 in pathological angiogenesis of the mouse retina. , 2007, The Journal of clinical investigation.

[99]  Jesper Z. Haeggström,et al.  Structural basis for synthesis of inflammatory mediators by human leukotriene C4 synthase , 2007, Nature.

[100]  R. Murphy,et al.  Biosynthesis and metabolism of leukotrienes. , 2007, The Biochemical journal.

[101]  S. Corbalán-García,et al.  Diacylglycerols, multivalent membrane modulators. , 2007, Chemistry and physics of lipids.

[102]  A. Futerman,et al.  The metabolism and function of sphingolipids and glycosphingolipids , 2007, Cellular and Molecular Life Sciences.

[103]  J. Boyce Mast cells and eicosanoid mediators: a system of reciprocal paracrine and autocrine regulation , 2007, Immunological reviews.

[104]  R. Neubert,et al.  Separation and mass spectrometric characterization of covalently bound skin ceramides using LC/APCI-MS and Nano-ESI-MS/MS. , 2007, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[105]  A. Postle,et al.  Probing phospholipid dynamics by electrospray ionisation mass spectrometry. , 2007, Progress in lipid research.

[106]  Don-On Daniel Mak,et al.  Inositol trisphosphate receptor Ca2+ release channels. , 2007, Physiological reviews.

[107]  S. Nigam,et al.  Biochemistry and pharmacology of endovanilloids. , 2007, Pharmacology & therapeutics.

[108]  Charles N. Serhan,et al.  Resolvin E1 Selectively Interacts with Leukotriene B4 Receptor BLT1 and ChemR23 to Regulate Inflammation1 , 2007, The Journal of Immunology.

[109]  J. Gutkind,et al.  G-protein-coupled receptors and cancer , 2007, Nature Reviews Cancer.

[110]  E. Israel,et al.  Protectin D1 Is Generated in Asthma and Dampens Airway Inflammation and Hyperresponsiveness1 , 2007, The Journal of Immunology.

[111]  Edward A Dennis,et al.  The phospholipase A2 superfamily and its group numbering system. , 2006, Biochimica et biophysica acta.

[112]  S. Payne,et al.  Role of ABCC1 in export of sphingosine-1-phosphate from mast cells , 2006, Proceedings of the National Academy of Sciences.

[113]  Pietro De Camilli,et al.  Phosphoinositides in cell regulation and membrane dynamics , 2006, Nature.

[114]  W. von Scheidt,et al.  Prostaglandin E1 testing in heart failure-associated pulmonary hypertension enables transplantation: the PROPHET study. , 2006, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[115]  P. Pacher,et al.  The Endocannabinoid System as an Emerging Target of Pharmacotherapy , 2006, Pharmacological Reviews.

[116]  R. Busse,et al.  Cytochrome P450 Epoxygenase Gene Function in Hypoxic Pulmonary Vasoconstriction and Pulmonary Vascular Remodeling , 2006, Hypertension.

[117]  R. Ransohoff,et al.  The many roles of chemokines and chemokine receptors in inflammation. , 2006, The New England journal of medicine.

[118]  K. Druey,et al.  Prostaglandin E2 Promotes Colon Cancer Cell Growth Through a Gs-Axin-ß-Catenin Signaling Axis , 2005, Science.

[119]  R. Murphy,et al.  Electrospray ionization and tandem mass spectrometry of eicosanoids. , 2005, Analytical biochemistry.

[120]  C. Serhan,et al.  Anti-inflammatory circuitry: lipoxin, aspirin-triggered lipoxins and their receptor ALX. , 2005, Prostaglandins, leukotrienes, and essential fatty acids.

[121]  M. Wenk The emerging field of lipidomics , 2005, Nature Reviews Drug Discovery.

[122]  J. Chun,et al.  S1P3 receptor-induced reorganization of epithelial tight junctions compromises lung barrier integrity and is potentiated by TNF. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[123]  A. Merrill,et al.  Sphingolipidomics: high-throughput, structure-specific, and quantitative analysis of sphingolipids by liquid chromatography tandem mass spectrometry. , 2005, Methods.

[124]  T. Bisogno,et al.  The endocannabinoid signalling system: Biochemical aspects , 2005, Pharmacology Biochemistry and Behavior.

[125]  R. Capasso,et al.  Involvement of the cannabimimetic compound, N-palmitoyl-ethanolamine, in inflammatory and neuropathic conditions: Review of the available pre-clinical data, and first human studies , 2005, Neuropharmacology.

[126]  Xianlin Han,et al.  Shotgun lipidomics: electrospray ionization mass spectrometric analysis and quantitation of cellular lipidomes directly from crude extracts of biological samples. , 2005, Mass spectrometry reviews.

[127]  P. Comfurius,et al.  Surface exposure of phosphatidylserine in pathological cells , 2005, Cellular and Molecular Life Sciences CMLS.

[128]  Xianlin Han,et al.  Shotgun lipidomics: multidimensional MS analysis of cellular lipidomes , 2005, Expert review of proteomics.

[129]  R. Breyer,et al.  Pharmacology and signaling of prostaglandin receptors: multiple roles in inflammation and immune modulation. , 2004, Pharmacology & therapeutics.

[130]  J. Chun,et al.  Lysophospholipid receptors: signaling and biology. , 2004, Annual review of biochemistry.

[131]  Y. Hannun,et al.  Sphingolipids in inflammation: roles and implications. , 2004, Current molecular medicine.

[132]  R. Proia,et al.  Transactivation of Sphingosine-1–Phosphate Receptors by FcɛRI Triggering Is Required for Normal Mast Cell Degranulation and Chemotaxis , 2004, The Journal of experimental medicine.

[133]  C. Serhan,et al.  Resolvins, docosatrienes, and neuroprotectins, novel omega-3-derived mediators, and their aspirin-triggered endogenous epimers: an overview of their protective roles in catabasis. , 2004, Prostaglandins & other lipid mediators.

[134]  L. Petrocellis,et al.  The endocannabinoid system: a general view and latest additions , 2004, British journal of pharmacology.

[135]  Ivo Feussner,et al.  The lipoxygenase pathway. , 2003, Annual review of plant biology.

[136]  R. Murphy,et al.  Electrospray mass spectrometry of phospholipids. , 2003, Mass spectrometry reviews.

[137]  A. Habib,et al.  Thromboxane prostanoid receptor in human airway smooth muscle cells: a relevant role in proliferation. , 2003, European journal of pharmacology.

[138]  G. Mills,et al.  The emerging role of lysophosphatidic acid in cancer , 2003, Nature Reviews Cancer.

[139]  Korey R. Johnson,et al.  The sphingosine kinase 1/sphingosine‐1‐phosphate pathway mediates COX‐2 induction and PGE2 production in response to TNF‐α , 2003 .

[140]  B. Matuszewski,et al.  Strategies for the assessment of matrix effect in quantitative bioanalytical methods based on HPLC-MS/MS. , 2003, Analytical chemistry.

[141]  K. Waku,et al.  Ether‐linked analogue of 2‐arachidonoylglycerol (noladin ether) was not detected in the brains of various mammalian species , 2003, Journal of neurochemistry.

[142]  J. Chambers,et al.  The Orphan G Protein-coupled Receptor GPR40 Is Activated by Medium and Long Chain Fatty Acids* , 2003, The Journal of Biological Chemistry.

[143]  F. Ruschitzka,et al.  Selective COX-2 Inhibition Improves Endothelial Function in Coronary Artery Disease , 2003, Circulation.

[144]  G. Zimmerman,et al.  Platelet-Activating Factor, a Pleiotrophic Mediator of Physiological and Pathological Processes , 2003, Critical reviews in clinical laboratory sciences.

[145]  M. Dohadwala,et al.  Autocrine/Paracrine Prostaglandin E2 Production by Non-small Cell Lung Cancer Cells Regulates Matrix Metalloproteinase-2 and CD44 in Cyclooxygenase-2-dependent Invasion* , 2002, The Journal of Biological Chemistry.

[146]  J. C. Hinshaw,et al.  Identification of an intracellular receptor for lysophosphatidic acid (LPA): LPA is a transcellular PPARγ agonist , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[147]  P. Chanez,et al.  15-lipoxygenase: a Janus enzyme? , 2002, American journal of respiratory cell and molecular biology.

[148]  D. Denis,et al.  The Immunomodulatory Actions of Prostaglandin E2 on Allergic Airway Responses in the Rat1 , 2002, The Journal of Immunology.

[149]  B. Hammock,et al.  The simultaneous quantification of cytochrome P450 dependent linoleate and arachidonate metabolites in urine by HPLC-MS/MS DOI 10.1194/jlr.D200018-JLR200 , 2002, Journal of Lipid Research.

[150]  P. O'Byrne,et al.  Cysteinyl leukotrienes promote human airway smooth muscle migration. , 2002, American journal of respiratory and critical care medicine.

[151]  Eugene Y. Kim,et al.  Multi-pronged inhibition of airway hyper-responsiveness and inflammation by lipoxin A4 , 2002, Nature Medicine.

[152]  J. Balsinde,et al.  Roles of various phospholipases A2 in providing lysophospholipid acceptors for fatty acid phospholipid incorporation and remodelling. , 2002, The Biochemical journal.

[153]  F. Bymaster,et al.  Characterization of a novel endocannabinoid, virodhamine, with antagonist activity at the CB1 receptor. , 2002, The Journal of pharmacology and experimental therapeutics.

[154]  E. Goetzl,et al.  Lysophospholipids and their G protein-coupled receptors in inflammation and immunity. , 2002, Biochimica et biophysica acta.

[155]  M. Blute,et al.  Rationale for combination therapy of intraurethral prostaglandin E1 and sildenafil in the salvage of erectile dysfunction patients desiring noninvasive therapy , 2002, International Journal of Impotence Research.

[156]  R. Millar,et al.  Cyclooxygenase-1 is up-regulated in cervical carcinomas: autocrine/paracrine regulation of cyclooxygenase-2, prostaglandin e receptors, and angiogenic factors by cyclooxygenase-1. , 2002, Cancer research.

[157]  M. Nishizawa,et al.  Central nociceptive role of prostacyclin (IP) receptor induced by peripheral inflammation , 2002, Neuroreport.

[158]  C. Funk,et al.  Prostaglandins and leukotrienes: advances in eicosanoid biology. , 2001, Science.

[159]  T. Eling,et al.  15-Lipoxygenase-1 Metabolites Down-regulate Peroxisome Proliferator-activated Receptor γ via the MAPK Signaling Pathway* , 2001, The Journal of Biological Chemistry.

[160]  R. Poduri,et al.  Cysteinyl leukotrienes mediate enhanced vasoconstriction to angiotensin II but not endothelin-1 in SHR. , 2001, American journal of physiology. Heart and circulatory physiology.

[161]  S. Narumiya,et al.  Characterization of EP receptor subtypes responsible for prostaglandin E2‐induced pain responses by use of EP1 and EP3 receptor knockout mice , 2001, British journal of pharmacology.

[162]  A. Sala,et al.  Neutrophils, endothelial cells, and cysteinyl leukotrienes: a new approach to neutrophil-dependent inflammation? , 2001, Biochemical and biophysical research communications.

[163]  H. Bisgaard Pathophysiology of the cysteinyl leukotrienes and effects of leukotriene receptor antagonists in asthma , 2001, Allergy.

[164]  R. Kostiainen,et al.  Quantitative determination of phospholipid compositions by ESI-MS: effects of acyl chain length, unsaturation, and lipid concentration on instrument response. , 2001, Journal of lipid research.

[165]  Z. Vogel,et al.  2-Arachidonyl glyceryl ether, an endogenous agonist of the cannabinoid CB1 receptor , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[166]  C. Woolf,et al.  Direct Activation of Rat Spinal Dorsal Horn Neurons by Prostaglandin E2 , 2001, The Journal of Neuroscience.

[167]  Jesper Z. Haeggström,et al.  Crystal structure of human leukotriene A4 hydrolase, a bifunctional enzyme in inflammation , 2001, Nature Structural Biology.

[168]  H. Hansen,et al.  N-Acylethanolamines and precursor phospholipids - relation to cell injury. , 2000, Chemistry and physics of lipids.

[169]  L. Petrocellis,et al.  N-acyl-dopamines: novel synthetic CB(1) cannabinoid-receptor ligands and inhibitors of anandamide inactivation with cannabimimetic activity in vitro and in vivo. , 2000, The Biochemical journal.

[170]  S T Holgate,et al.  Altered airway surfactant phospholipid composition and reduced lung function in asthma. , 2000, Journal of applied physiology.

[171]  B. Samuelsson The discovery of the leukotrienes. , 2000, American journal of respiratory and critical care medicine.

[172]  K. Waku,et al.  Evidence That 2-Arachidonoylglycerol but Not N-Palmitoylethanolamine or Anandamide Is the Physiological Ligand for the Cannabinoid CB2 Receptor , 2000, The Journal of Biological Chemistry.

[173]  W. Lands,et al.  Stories about acyl chains. , 2000, Biochimica et biophysica acta.

[174]  R. Veldhuizen,et al.  The role of lipids in pulmonary surfactant. , 1998, Biochimica et biophysica acta.

[175]  P. Lipsky,et al.  Cyclooxygenase in biology and disease , 1998, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[176]  D. Zeldin,et al.  Epoxygenase metabolites of arachidonic acid affect electrophysiologic properties of rat tracheal epithelial cells1. , 1998, The Journal of pharmacology and experimental therapeutics.

[177]  K. Waku,et al.  2‐Arachidonoylglycerol, an endogenous cannabinoid receptor agonist: identification as one of the major species of monoacylglycerols in various rat tissues, and evidence for its generation through Ca2+‐dependent and ‐independent mechanisms , 1998, FEBS letters.

[178]  R. Kim,et al.  A 12R-lipoxygenase in human skin: mechanistic evidence, molecular cloning, and expression. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[179]  Thea Koch,et al.  Lipid Mediators in Inflammatory Disorders , 1998, Drugs.

[180]  M. Zenk,et al.  Biological activity and biosynthesis of pentacyclic oxylipins: The linoleic acid pathway , 1998 .

[181]  G. van Echten-Deckert,et al.  Conversion of dihydroceramide to ceramide occurs at the cytosolic face of the endoplasmic reticulum , 1997, FEBS letters.

[182]  S. Narumiya,et al.  Altered pain perception and inflammatory response in mice lacking prostacyclin receptor , 1997, Nature.

[183]  K. Schrör Aspirin and Platelets: The Antiplatelet Action of Aspirin and Its Role in Thrombosis Treatment and Prophylaxis , 1997, Seminars in thrombosis and hemostasis.

[184]  S D Hall,et al.  Regioselective and stereoselective metabolism of ibuprofen by human cytochrome P450 2C. , 1997, Biochemical pharmacology.

[185]  E. Ikonen,et al.  Functional rafts in cell membranes , 1997, Nature.

[186]  Peter J. Brown,et al.  Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors α and γ , 1997 .

[187]  A. Schroit,et al.  Pathophysiologic implications of membrane phospholipid asymmetry in blood cells. , 1997, Blood.

[188]  B. Borhan,et al.  Novel metabolic pathways for linoleic and arachidonic acid metabolism. , 1996, Biochimica et biophysica acta.

[189]  C. Andresen,et al.  In vitro and in vivo effects of leukotriene B4 antagonism in a primate model of asthma. , 1996, The Journal of clinical investigation.

[190]  M. Triggiani,et al.  Control of arachidonate levels within inflammatory cells. , 1996, Biochimica et biophysica acta.

[191]  A. Yamashita,et al.  2-Arachidonoylglycerol: a possible endogenous cannabinoid receptor ligand in brain. , 1995, Biochemical and biophysical research communications.

[192]  N. Godessart,et al.  Interleukin-1 Enhances the Ability of Cultured Human Umbilical Vein Endothelial Cells to Oxidize Linoleic Acid (*) , 1995, The Journal of Biological Chemistry.

[193]  Z. Vogel,et al.  Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. , 1995, Biochemical pharmacology.

[194]  T. Casale,et al.  5-Hydroxyeicosatetraenoic acid (HETE)-induced neutrophil transcellular migration is dependent upon enantiomeric structure. , 1995, American journal of respiratory cell and molecular biology.

[195]  R. Roman,et al.  Role of cytochrome P-450 enzymes and metabolites of arachidonic acid in the control of vascular tone. , 1995, Journal of Vascular Research.

[196]  H. Herschman,et al.  Regulation of prostaglandin synthase-1 and prostaglandin synthase-2 , 1994, Cancer and Metastasis Reviews.

[197]  S. Almog,et al.  Two new unsaturated fatty acid ethanolamides in brain that bind to the cannabinoid receptor. , 1993, Journal of medicinal chemistry.

[198]  D. Gibson,et al.  Isolation and structure of a brain constituent that binds to the cannabinoid receptor. , 1992, Science.

[199]  G. Baxter,et al.  In vitro characterization of prostanoid FP‐, DP‐, IP‐ and TP‐receptors on the non‐pregnant human myometrium , 1992, British journal of pharmacology.

[200]  S. Dahlén,et al.  Urinary excretion of leukotriene E4 and 11-dehydro-thromboxane B2 in response to bronchial provocations with allergen, aspirin, leukotriene D4, and histamine in asthmatics. , 1992, The American review of respiratory disease.

[201]  H. Jacobson,et al.  Glomerular stereospecific synthesis and hemodynamic actions of 8,9-epoxyeicosatrienoic acid in rat kidney. , 1991, The American journal of physiology.

[202]  F. A. Green,et al.  Stereospecificity of the hydroxyeicosatetraenoic and hydroxyoctadecadienoic acids produced by cultured bovine endothelial cells. , 1991, Biochimica et biophysica acta.

[203]  S. Nakanishi,et al.  Cloning and expression of cDNA for a human thromboxane A2 receptor , 1991, Nature.

[204]  N. Salem,et al.  Separation of lipid classes by solid phase extraction. , 1990, Journal of lipid research.

[205]  Robert A. Lewis,et al.  Leukotrienes and other products of the 5-lipoxygenase pathway. Biochemistry and relation to pathobiology in human diseases. , 1990, The New England journal of medicine.

[206]  A. Black,et al.  The release of prostaglandin D2 from human skin in vivo and in vitro during immediate allergic reactions , 1988, British journal of pharmacology.

[207]  S. Dahlén,et al.  Leukotrienes and lipoxins: structures, biosynthesis, and biological effects. , 1987, Science.

[208]  P. J. Gardiner,et al.  Characterization of prostanoid relaxant/inhibitory receptors (ψ) using a highly selective agonist, TR4979 , 1986, British journal of pharmacology.

[209]  M. Hamberg,et al.  Lipoxins: novel series of biologically active compounds formed from arachidonic acid in human leukocytes. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[210]  S. Holgate,et al.  The bronchoconstrictor effect of inhaled prostaglandin D2 in normal and asthmatic men. , 1984, The New England journal of medicine.

[211]  R. England,et al.  Acid-catalyzed transformation of 13(S)-hydroperoxylinoleic acid into epoxyhydroxyoctadecenoic and trihydroxyoctadecenoic acids , 1984 .

[212]  W. Stenson,et al.  Enhanced synthesis of leukotriene B4 by colonic mucosa in inflammatory bowel disease. , 1984, Gastroenterology.

[213]  R. Egan,et al.  Prostaglandins, arachidonic acid, and inflammation. , 1980, Science.

[214]  I. Mackenzie,et al.  A COMPARISON OF PGE2 AND PGF2α VAGINAL GEL FOR RIPENING THE CERVIX BEFORE INDUCTION OF LABOUR , 1979 .

[215]  P. Abrams,et al.  The actions of prostaglandins on the smooth muscle of the human urinary tract in vitro. , 1975, British journal of urology.

[216]  M. Hamberg,et al.  On the Metabolism of Prostaglandins E1 and E2 in Man , 1971 .

[217]  S. Wendlandt,et al.  Effects on body temperature of prostaglandins of the A, E and F series on injection into the third ventricle of unanaesthetized cats and rabbits , 1971, The Journal of physiology.

[218]  W. J. Dyer,et al.  A rapid method of total lipid extraction and purification. , 1959, Canadian journal of biochemistry and physiology.

[219]  J. Folch,et al.  A simple method for the isolation and purification of total lipides from animal tissues. , 1957, The Journal of biological chemistry.

[220]  C. Lyketsos,et al.  Plasma sphingomyelins are associated with cognitive progression in Alzheimer's disease. , 2011, Journal of Alzheimer's disease : JAD.

[221]  B. Hammock,et al.  Use of metabolomic profiling in the study of arachidonic acid metabolism in cardiovascular disease. , 2011, Congestive heart failure.

[222]  A. Jadhav,et al.  Discovery of potent and selective inhibitors of human reticulocyte 15-lipoxygenase-1. , 2010, Journal of medicinal chemistry.

[223]  J. Egido,et al.  Leukotriene B4 enhances the activity of nuclear factor-kappaB pathway through BLT1 and BLT2 receptors in atherosclerosis. , 2009, Cardiovascular research.

[224]  G. FitzGerald,et al.  Noninvasive assessment of the role of cyclooxygenases in cardiovascular health: a detailed HPLC/MS/MS method. , 2007, Methods in enzymology.

[225]  R. Capasso,et al.  Role and regulation of acylethanolamides in energy balance: focus on adipocytes and beta-cells. , 2007, British journal of pharmacology.

[226]  A. Merrill,et al.  Structure-specific, quantitative methods for analysis of sphingolipids by liquid chromatography-tandem mass spectrometry: "inside-out" sphingolipidomics. , 2007, Methods in enzymology.

[227]  G. Sparagna,et al.  Role of cardiolipin alterations in mitochondrial dysfunction and disease. , 2007, American journal of physiology. Cell physiology.

[228]  Tom S. Price,et al.  Marked interindividual variability in the response to selective inhibitors of cyclooxygenase-2. , 2006, Gastroenterology.

[229]  Mitra Poulami,et al.  マスト細胞からのスフィンゴシン‐1‐りん酸の運び出しに果たすABCC1の役割 , 2006 .

[230]  B. Hammock,et al.  Epoxide hydrolases: their roles and interactions with lipid metabolism. , 2005, Progress in lipid research.

[231]  Xiang Fang,et al.  Epoxyeicosatrienoic acids (EETs): metabolism and biochemical function. , 2004, Progress in lipid research.

[232]  R. Roman,et al.  P-450 metabolites of arachidonic acid in the control of cardiovascular function. , 2002, Physiological reviews.

[233]  E. Jacobs,et al.  The lung HETEs (and EETs) up. , 2001, American journal of physiology. Heart and circulatory physiology.

[234]  D. Zeldin,et al.  Metabolism of epoxyeicosatrienoic acids by cytosolic epoxide hydrolase: substrate structural determinants of asymmetric catalysis. , 1995, Archives of biochemistry and biophysics.

[235]  H. Schmid,et al.  N-acylated glycerophospholipids and their derivatives. , 1990, Progress in lipid research.

[236]  F. Snyder Platelet-Activating Factor and Related Lipid Mediators , 1987, Springer US.

[237]  Kai Simons,et al.  Automated identification and quantification of glycerophospholipid molecular species by multiple precursor ion scanning. , 2006, Analytical chemistry.