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Prostaglandins may be considered as derivatives of prostanoic acid, though prostanoic acid does not naturally occur in the body.
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Leukotrienes are named so because they were first obtained from leukocytes.
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Eicosanoids are the most universally distributed autacoids in the body. Practically every cell and tissue is capable of synthesizing one or more types of prostaglandins or leukotrienes.
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There are no preformed stores of prostaglandins and leukotrienes.
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They are synthesized locally at rates governed by the release of arachidonic acid from membrane lipids in response to appropriate stimuli.
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These stimuli activate hydrolases including phospholipase A2, probably through increased intracellular Ca++.
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The cycloxygenase (COX) pathway generates eicosanoids with a ring structure (PGs, TXs, prostacyclin) and lipoxygenase (LOX) produce open chain compounds (LTs).
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All tissues have COX – can form cyclic endoperoxides PGG2 and PGH2, which are unstable compounds. PGE2 and PGF2α are the primary prostaglandins.
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PGs A, B and C are not found in the body.
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They are artifacts formed during extraction procedures. Lung and spleen can synthesize the whole range of cycloxygenase products. Platelets primarily synthesize TXA2 which is chemically unstable, spontaneously changes to TXB2.
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Vessel wall mainly generates prostacyclin (PGI2), also chemically unstable.
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Cycloxygenase exists in two forms – COX1 and COX2.
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Eicosanoids produced by COX1 participate in physiological functions such as secretion of mucus for protection of gastric mucosa, homeostasis and maintenance of renal functions, while those produced by COX2 lead to inflammatory and other pathological changes.
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COX1 is a constitutive form found in the mast cells. It is continuously forming prostaglandins in small amounts.
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COX2 is induced in inflammatory cells in response to inflammatory stimulus. Its formation is induced by signals (mainly inflammatory).
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It produces very high levels of prostaglandins in a short amount of time (compared to COX1 which produces small amounts over a prolonged time).
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The prostaglandins produced are only released during pathological conditions.
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Aspirin is selelctive COX1 inhibitor and nabumetone, meloxicam and nimesulide are selective COX2 inhibitors.
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Lipoxygenase pathway appears to operate mainly in the lung, WBC and platelets.
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Its most important products are leukotrienes, particularly LTB4 (potent chemotactic) and LTC4, LTD4, which together constitute the slow reacting substance of anaphylaxis (SRS-A).