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Acta Medica Austriaca 1977The physiologic and pathophysiologic role of the prostaglandins in the lung is not fully understood. Prostaglandins seem to be important in the regulation of local blood... (Review)
Review
The physiologic and pathophysiologic role of the prostaglandins in the lung is not fully understood. Prostaglandins seem to be important in the regulation of local blood flow. They might be involved in relaxation of the pulmonary vascular bed by opposing hypoxic pulmonary vasoconstriction and in constriction of the pulmonary vascular bed after microembolisation. The tonus of bronchial muscle is also probably modulated by the prostaglandins. Prostaglandin degradation in the lung might be another physiological role of lung function, which would allow the regulation of arterial blood levels. It is not known if this is of importance for the regulation of systemic, or other local circulations. If prostaglandins are primarily involved in patients with asthma is not clear, secondary effects at least, are probable. The therapeutic aspects of exogen administered prostaglandins are thus far of little clinical importance for the lung.
Topics: Asthma; Blood Platelets; Bronchodilator Agents; Humans; Hypoxia; Lung; Muscle Tonus; Muscle, Smooth; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Prostaglandins F; Pulmonary Circulation
PubMed: 418617
DOI: No ID Found -
Prostaglandins & Other Lipid Mediators Aug 2002Prostanoids are a group of lipid mediators that include the prostaglandins (PG) and thromboxanes (TX). Upon cell stimulation, prostanoids are synthesized from... (Review)
Review
Prostanoids are a group of lipid mediators that include the prostaglandins (PG) and thromboxanes (TX). Upon cell stimulation, prostanoids are synthesized from arachidonic acid via the cyclooxygenase (COX) pathway and released outside the cells to exert various physiological and pathological actions in a variety of tissues and cells. The activities of prostanoids are mediated by specific G protein-coupled receptors, which have been classified on the basis of pharmacological experiments into eight types and subtypes according to their responsiveness to selective agonists and antagonists. These prostanoid receptors have been cloned from various species including human, and their distinct binding properties and signal transduction pathways have been characterized by analyses of cells expressing each receptor. Furthermore, the distribution patterns of prostanoid receptor mRNAs have been determined in tissues and cells for various species. This information is useful for understanding the molecular basis of the pathophysiological actions of prostanoids.
Topics: Animals; Gene Expression Regulation; Humans; Ligands; Molecular Structure; Prostaglandins; Protein Binding; Protein Isoforms; Receptors, Prostaglandin; Signal Transduction; Tissue Distribution
PubMed: 12432942
DOI: 10.1016/s0090-6980(02)00054-0 -
Prostaglandins, Leukotrienes, and... Nov 1992
Review
Topics: Adipose Tissue; Animals; Feedback; Humans; Lipolysis; Prostaglandins; Receptors, Prostaglandin
PubMed: 1475271
DOI: 10.1016/0952-3278(92)90235-b -
FASEB Journal : Official Publication of... Jul 1999Prostaglandins and NO. are important mediators of inflammation and other physiological and pathophysiological processes. Continuous production of these molecules in... (Review)
Review
Prostaglandins and NO. are important mediators of inflammation and other physiological and pathophysiological processes. Continuous production of these molecules in chronic inflammatory conditions has been linked to development of autoimmune disorders, coronary artery disease, and cancer. There is mounting evidence for a biological relationship between prostanoid biosynthesis and NO. biosynthesis. Upon stimulation, many cells express high levels of nitric oxide synthase (NOS) and prostaglandin endoperoxide synthase (PGHS). There are reports of stimulation of prostaglandin biosynthesis in these cells by direct interaction between NO. and PGHS, but this is not universally observed. Clarification of the role of NO. in PGHS catalysis has been attempted by examining NO. interactions with purified PGHS, including binding to its heme prosthetic group, cysteines, and tyrosyl radicals. However, a clear picture of the mechanism of PGHS stimulation by NO. has not yet emerged. Available studies suggest that NO. may only be a precursor to the molecule that interacts with PGHS. Peroxynitrite (from O2.-+NO.) reacts directly with PGHS to activate prostaglandin synthesis. Furthermore, removal of O2.- from RAW 267.4 cells that produce NO. and PGHS inhibits prostaglandin biosynthesis to the same extent as NOS inhibitors. This interaction between reactive nitrogen species and PGHS may provide new approaches to the control of inflammation in acute and chronic settings.
Topics: Animals; Enzyme Activation; Nitrates; Nitric Oxide; Prostaglandin-Endoperoxide Synthases; Prostaglandins
PubMed: 10385604
DOI: 10.1096/fasebj.13.10.1121 -
The Journal of Biological Chemistry Aug 2005Prostaglandins mediate autacrine and paracrine signaling over short distances. We used the renal collecting duct as a model system to test the hypothesis that local...
Prostaglandins mediate autacrine and paracrine signaling over short distances. We used the renal collecting duct as a model system to test the hypothesis that local control of prostaglandin signaling is achieved by expressing inactivation in the same cell as synthesis. Immunocytochemical studies demonstrated that renal collecting ducts in situ express the prostaglandin (PG) synthesis enzyme, cyclooxygenase-1 (COX-1), as well as both components of prostaglandin metabolic inactivation, i.e. the prostaglandin uptake carrier prostaglandin transporter (PGT) and the enzyme 15-hydroxyprostaglandin dehydrogenase. We characterized this system further using the collecting duct cell line Madin-Darby canine kidney (MDCK), which retains COX-2 and prostaglandin dehydrogenase expression but which has lost PGT expression. When we reintroduced PGT, it was correctly sorted to the apical membrane where it altered the sidedness of prostaglandin E2 (PGE2) release, a process we call "vectorial release via sided reuptake." Importantly, although COX-2 and prostaglandin dehydrogenase are expressed in the same MDCK cell, they must be compartmentalized because even in the presence of excess dehydrogenase newly synthesized PGE2 is released largely un-oxidized. However, when PGE2 undergoes first release and then PGT-mediated reuptake, significant oxidation takes place, suggesting that PGT imports PGE2 into the prostaglandin dehydrogenase compartment. Our data are consistent with a new model that offers significant new mechanisms for the fine control of eicosanoid signaling.
Topics: Animals; Cell Line; Cyclooxygenase 1; Cyclooxygenase 2; Dogs; Kidney Tubules, Collecting; Male; Membrane Proteins; Oxidation-Reduction; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Rats; Rats, Sprague-Dawley; Signal Transduction
PubMed: 15855165
DOI: 10.1074/jbc.M408286200 -
Biochimica Et Biophysica Acta Jun 1980Arachidonic acid and prostaglandin H2 elevate the levels of adenosine 3':5'-monophosphate (cyclic AMP) in Balb/c 3T3 fibroblasts. This effect was inhibited by...
Arachidonic acid and prostaglandin H2 elevate the levels of adenosine 3':5'-monophosphate (cyclic AMP) in Balb/c 3T3 fibroblasts. This effect was inhibited by 15-hydroperoxy-5,8,11,13-eicosatetraenoic acid, an inhibitor of prostaglandin I2 synthase (Claesson, H.-E., Lindgren, J.A. and Hammarstr!om, S. (1977) FEBS Lett. 81, 415-418). After addition of arachidonic acid to 3T3 cultures, cellular cyclic AMP levels and growth medium concentrations of 6-ketoprostaglandin F1 alpha (degradation product of prostaglandin I2) were quantitatively determined. The stimulatory effect of exogenously-added prostaglandin I2 on cellular cyclic AMP levels was also determined. The results indicate that the endogenous production of prostaglandin I2 is sufficient to explain the stimulatory action of arachidonic acid on cyclic AMP formation in 3T3 fibroblasts.
Topics: 6-Ketoprostaglandin F1 alpha; Animals; Arachidonic Acids; Cells, Cultured; Cyclic AMP; Epoprostenol; Fibroblasts; Mice; Mice, Inbred BALB C; Platelet Aggregation; Prostaglandins; Prostaglandins F; Prostaglandins H
PubMed: 6249378
DOI: 10.1016/0005-2760(80)90258-1 -
Journal of Steroid Biochemistry 1987Glucocorticoids induce the synthesis of a family of phospholipase inhibitory proteins, lipocortins. This family of lipocortins includes inhibitory proteins on... (Review)
Review
Glucocorticoids induce the synthesis of a family of phospholipase inhibitory proteins, lipocortins. This family of lipocortins includes inhibitory proteins on phospholipase A2, phospholipase C and phosphatidylinositol phospholipase C. Hence, glucocorticoids reduce the formation of prostaglandins and leukotrienes by inhibiting cellular phospholipases, enzymes that degrade membrane phospholipids to release arachidonic acid, a precursor. The induction by glucocorticoids requires 1 h for the synthesis of mRNA and 5 h for the synthesis of proteins in various tissues and cells. However, glucocorticoids often exert their suppressive effects before the induction of lipocortins. This is now attributed to the nonenzymic formation of the adducts between glucocorticoids and lipocortins. These adducts are easily inserted into the membranes and more resistant to digestion of proteases, thus being more biologically potent with respect to suppression of the release of arachidonic acid, a precursor of prostaglandins and leukotrienes.
Topics: Animals; Annexins; Glucocorticoids; Glycoproteins; Phospholipids; Prostaglandins; Protein Processing, Post-Translational
PubMed: 2961939
DOI: 10.1016/0022-4731(87)90189-0 -
Pathobiology Annual 1972
Review
Topics: Animals; Biological Transport, Active; Corpus Luteum; Fatty Acids, Essential; Fatty Acids, Nonesterified; Female; Fertilization; Humans; Hydrogen-Ion Concentration; Hypertension; Inflammation; Lipid Metabolism; Male; Mixed Function Oxygenases; Pregnancy; Prostaglandins; Spermatozoa; Structure-Activity Relationship; Water-Electrolyte Balance
PubMed: 4589748
DOI: No ID Found -
Pharmacological Reviews Mar 1968
Review
Topics: Animals; Carbohydrate Metabolism; Cardiovascular System; Humans; Lipid Metabolism; Muscle, Smooth; Nervous System; Prostaglandins; Urogenital System
PubMed: 4873508
DOI: No ID Found -
Brain Research Oct 1986We examined the brain uptake of prostaglandin D2 after its i.v. administration to mice. The determination of this prostaglandin in tissues was performed by a sensitive...
We examined the brain uptake of prostaglandin D2 after its i.v. administration to mice. The determination of this prostaglandin in tissues was performed by a sensitive and rapid radioimmunoassay after purification of the prostaglandin by high-performance liquid chromatography. When 1.0 mg/kg of prostaglandin D2 was injected, it was detectable in the brain 30 s after its administration (44 ng/g brain, about 0.08% of the administered dose). Brain uptake of prostaglandin D2 was dose-dependent over the dose range from 0.1 to 1.0 mg/kg and its half-life in the brain and blood was 1.1 and 0.9 min, respectively. The brain/blood ratio of the prostaglandin D2 concentration was 0.03 at 30 s and gradually increased to 0.2 during the first 15 min. These results suggest that prostaglandin D2 is taken up intact by the brain and disappears rapidly. Studies on the metabolic fate of tritium-labeled prostaglandin D2 revealed that it was a major component at 1 min, was metabolized to a number of hydrophilic and hydrophobic substances in the brain, whereas it was metabolized to mainly hydrophilic substances in the blood at 6 and 15 min, and the total radioactivities were cleared from the brain and blood with half-lives of 1.6 and 1.5 min, respectively.
Topics: Animals; Blood-Brain Barrier; Brain; Brain Chemistry; Chromatography, High Pressure Liquid; Injections, Intravenous; Mice; Prostaglandin D2; Prostaglandins D; Radioimmunoassay
PubMed: 3465420
DOI: 10.1016/0006-8993(86)91079-6