Regulation of pulmonary arachidonic acid metabolism by anti-inflammatory steroids.
Enzymes in cells from many tissues including the lung metabolize arachidonic acid to a variety of highly active local hormones such as prostaglandins and 'slow-reacting substances'. Many of these play a part in the inflammatory response which follows injury or trauma or, in the case of slow-reacting substance, asthmatic bronchoconstriction. Both non-steroidal and steroidal anti-inflammatory drugs inhibit the formation of some or all of these products. The non-steroidal drugs block prostaglandin formation but not the formation of products such as slow-reacting substances. The steroids block the formation of all products. Their mechanism of action, investigated in the guinea-pig perfused lung, involved inhibition of arachidonic acid liberation, probably by suppression of phospholipase activity. To achieve this steroids must first bind to receptors in lung tissue and initiate de novo RNA and protein synthesis. This culminates in the synthesis or secretion by some cells in the lung of a polypeptide of mol.wt. 10 000-15 000 with potent anti-phospholipase properties. The generation of this factor could partly explain why steroids are so effective in the treatment of many types of inflammatory disease, and in particular why they are so efficacious against asthma.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001095:Arachidonic Acids / Q000378:metabolism*; D004285:Dogs; D005938:Glucocorticoids / Q000494:pharmacology*; D006168:Guinea Pigs; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D010740:Phospholipases / Q000378:metabolism; D011449:Prostaglandin Endoperoxides / Q000378:metabolism; D013928:Thromboxane A2 / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D001095:Arachidonic Acids; D005938:Glucocorticoids; D011449:Prostaglandin Endoperoxides; D013928:Thromboxane A2; D010740:Phospholipases