プロスタグランジン—その生体内における位置づけと全体像
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Arachidonic acid metabolites, prostaglandins (PGs), thromboxanes (TXs), and leukotrienes (LTs), are classified as a type of autacoids. They are not stored in the cells, but stored as a precursor acid, arachidonic acid, in membrane phospholipids. Various physiological stimuli activate phospholipase A<SUB>2</SUB> and release arachidonic acid, which is converted to 1 or 2 products by related enzymes within a few minutes, depending upon individual cell functions. The metabolites are readily inactivated in aqueous solution and in the body. The structures of the various metabolites are quite similar, but their pharmacological actions vary from metabolite to metabolite and some exert opposite actions to those of others. The metabolites play some pivotal roles in physiological or pathophysiological responses such as pain sensation, fever, plasma leakage and skin erythema. Thus, non-steroidal anti-inflammatory drugs, like aspirin, exert their actions through cyclooxygenase inhibition at low doses. PGE<SUB>2</SUB> can be detected in the exudate of acute inflammatory models, and the simultaneous release of PGE<SUB>2</SUB> with bradykinin induces a large increase in plasma leakage and triggers exudate accumulation. LTB<SUB>4</SUB> induces extravasation of PMN leukocytes at the micro circulatory level and is generated in the reperfused area of infarcted cardiac tissue after ligation of rat coronary artery, but in the latter case, the leukocyte migration was not solely induced by LTB<SUB>4</SUB>, which was replaced by a complement component (C<SUB>5a</SUB>). LTC<SUB>4</SUB> may be involved in ethanol injury of the gastric mucosa and endogenous PGE<SUB>2</SUB> prevents this injury. The real roles of individual arachidonic acid metabolites have been gradually disclosed, but most of the roles are still yet to be clarified.
- 社団法人 日本薬理学会の論文
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