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Science 30 November 2001:
Vol. 294. no. 5548, pp. 1871 - 1875
DOI: 10.1126/science.294.5548.1871
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Review

Prostaglandins and Leukotrienes: Advances in Eicosanoid Biology

Colin D. Funk

Prostaglandins and leukotrienes are potent eicosanoid lipid mediators derived from phospholipase-released arachidonic acid that are involved in numerous homeostatic biological functions and inflammation. They are generated by cyclooxygenase isozymes and 5-lipoxygenase, respectively, and their biosynthesis and actions are blocked by clinically relevant nonsteroidal anti-inflammatory drugs, the newer generation coxibs (selective inhibitors of cyclooxygenase-2), and leukotriene modifiers. The prime mode of prostaglandin and leukotriene action is through specific G protein-coupled receptors, many of which have been cloned recently, thus enabling specific receptor agonist and antagonist development. Important insights into the mechanisms of inflammatory responses, pain, and fever have been gleaned from our current understanding of eicosanoid biology.

Center for Experimental Therapeutics and Department of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104, USA. E-mail: colin{at}spirit.gcrc.upenn.edu

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(n-6) PUFA Increase and Dairy Foods Decrease Prostate Cancer Risk in Heavy Smokers.
M. L. Neuhouser, M. J. Barnett, A. R. Kristal, C. B. Ambrosone, I. King, M. Thornquist, and G. Goodman (2007)
J. Nutr. 137, 1821-1827
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Identification of a Novel Prostaglandin Reductase Reveals the Involvement of Prostaglandin E2 Catabolism in Regulation of Peroxisome Proliferator-activated Receptor {gamma} Activation.
W.-L. Chou, L.-M. Chuang, C.-C. Chou, A. H.-J. Wang, J. A. Lawson, G. A. FitzGerald, and Z.-F. Chang (2007)
J. Biol. Chem. 282, 18162-18172
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Development of a Homogeneous Time-Resolved Fluorescence Leukotriene B4 Assay for Determining the Activity of Leukotriene A4 Hydrolase.
A. M. Liang, E. Claret, J. Ouled-Diaf, A. Jean, D. Vogel, D. R. Light, S. W. Jones, W. J. Guilford, J. F. Parkinson, and R. M. Snider (2007)
J Biomol Screen 12, 536-545
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Epoxyeicosatrienoic Acid Relaxing Effects Involve Ca2+-Activated K+ Channel Activation and CPI-17 Dephosphorylation in Human Bronchi.
C. Morin, M. Sirois, V. Echave, M. M. Gomes, and E. Rousseau (2007)
Am. J. Respir. Cell Mol. Biol. 36, 633-641
   Abstract »    Full Text »    PDF »
Placental-Perinatal: Effects of indomethacin on systemic and renal haemodynamics in conscious lambs.
K. K. Ebenezar, F. S. Ghane, and F. G. Smith (2007)
Exp Physiol 92, 575-581
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Function, Activity, and Membrane Targeting of Cytosolic Phospholipase A2{zeta} in Mouse Lung Fibroblasts.
M. Ghosh, R. Loper, F. Ghomashchi, D. E. Tucker, J. V. Bonventre, M. H. Gelb, and C. C. Leslie (2007)
J. Biol. Chem. 282, 11676-11686
   Abstract »    Full Text »    PDF »
The membrane and lipids as integral participants in signal transduction: lipid signal transduction for the non-lipid biochemist.
K. M. Eyster (2007)
Advan Physiol Educ 31, 5-16
   Abstract »    Full Text »    PDF »
Dose and Time-Dependent Effects of Cyclooxygenase-2 Inhibition on Fracture-Healing.
A. M. Simon and J. P. O'Connor (2007)
J. Bone Joint Surg. Am. 89, 500-511
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Dectin-1 Stimulation by Candida albicans Yeast or Zymosan Triggers NFAT Activation in Macrophages and Dendritic Cells.
H. S. Goodridge, R. M. Simmons, and D. M. Underhill (2007)
J. Immunol. 178, 3107-3115
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Action of epoxyeicosatrienoic acids on cellular function.
A. A. Spector and A. W. Norris (2007)
Am J Physiol Cell Physiol 292, C996-C1012
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Cyclooxygenase-1 Is Involved in Endothelial Dysfunction of Mesenteric Small Arteries From Angiotensin II-Infused Mice.
A. Virdis, R. Colucci, M. Fornai, E. Duranti, C. Giannarelli, N. Bernardini, C. Segnani, C. Ippolito, L. Antonioli, C. Blandizzi, et al. (2007)
Hypertension 49, 679-686
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Chemical Determinants Involved in Anandamide-induced Inhibition of T-type Calcium Channels.
J. Chemin, J. Nargeot, and P. Lory (2007)
J. Biol. Chem. 282, 2314-2323
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Targeted Cyclooxygenase Gene (Ptgs) Exchange Reveals Discriminant Isoform Functionality.
Y. Yu, J. Fan, Y. Hui, C. A. Rouzer, L. J. Marnett, A. J. Klein-Szanto, G. A. FitzGerald, and C. D. Funk (2007)
J. Biol. Chem. 282, 1498-1506
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Urinary Prostaglandin F2{alpha} Is Generated from the Isoprostane Pathway and Not the Cyclooxygenase in Humans.
H. Yin, L. Gao, H.-H. Tai, L. J. Murphey, N. A. Porter, and J. D. Morrow (2007)
J. Biol. Chem. 282, 329-336
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Inhibition of Cytokine Signaling in Human Retinal Endothelial Cells through Modification of Caveolae/Lipid Rafts by Docosahexaenoic Acid.
W. Chen, D. B. Jump, W. J. Esselman, and J. V. Busik (2007)
Invest. Ophthalmol. Vis. Sci. 48, 18-26
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Cyclic Adenosine 5'-Monophosphate-Stimulated Neurotensin Secretion Is Mediated through Rap1 Downstream of both Epac and Protein Kinase A Signaling Pathways.
J. Li, K. L. O'Connor, X. Cheng, F. C. Mei, T. Uchida, C. M. Townsend Jr, and B. M. Evers (2007)
Mol. Endocrinol. 21, 159-171
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Prostaglandin E2 Receptor EP4 Contributes to Inflammatory Pain Hypersensitivity.
C.-R. Lin, F. Amaya, L. Barrett, H. Wang, J. Takada, T. A. Samad, and C. J. Woolf (2006)
J. Pharmacol. Exp. Ther. 319, 1096-1103
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Prostacyclin Antagonism Reduces Pain and Inflammation in Rodent Models of Hyperalgesia and Chronic Arthritis.
A.-M. Pulichino, S. Rowland, T. Wu, P. Clark, D. Xu, M.-C. Mathieu, D. Riendeau, and L. P. Audoly (2006)
J. Pharmacol. Exp. Ther. 319, 1043-1050
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Nonenzymatic Lipid Peroxidation Reprograms Gene Expression and Activates Defense Markers in Arabidopsis Tocopherol-Deficient Mutants.
S. E. Sattler, L. Mene-Saffrane, E. E. Farmer, M. Krischke, M. J. Mueller, and D. DellaPenna (2006)
PLANT CELL 18, 3706-3720
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Lipopolysaccharide-induced Cyclooxygenase-2 Expression in Human U937 Macrophages Is Phosphatidic Acid Phosphohydrolase-1-dependent.
A. Grkovich, C. A. Johnson, M. W. Buczynski, and E. A. Dennis (2006)
J. Biol. Chem. 281, 32978-32987
   Abstract »    Full Text »    PDF »
Alleviating the Burden of Cancer: A Perspective on Advances, Challenges, and Future Directions..
D. Schottenfeld and J. Beebe-Dimmer (2006)
Cancer Epidemiol. Biomarkers Prev. 15, 2049-2055
   Abstract »    Full Text »    PDF »


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