Modes of action of aspirin-like drugs.
Current dogma holds that nonsteroidal anti-inflammatory drugs (NSAIDs) act by inhibition of the synthesis and release of prostaglandins. However, NSAIDs also inhibit the activation of neutrophils, which provoke inflammation by releasing products other than prostaglandins. We now report that NSAIDs (e.g., indomethacin, piroxicam) inhibit activation of neutrophils by inflammatory stimuli, such as C5-derived peptides and leukotriene B4, even when cyclooxygenase products generated in suspensions of stimulated neutrophils (prostaglandin E and thromboxanes) are present. Sodium salicylate (3 mM) greatly inhibited aggregation of neutrophils but had no effect on aggregation of platelets or production of thromboxane induced by arachidonate. Sodium salicylate and other NSAIDs also inhibit calcium movements (45Ca uptake, changes in fluorescence of chlortetracycline and quin-2). Aspirin, sodium salicylate, indomethacin, and piroxicam also enhanced the poststimulation increase in intracellular cyclic AMP. NSAIDs therefore inhibit early steps in neutrophil activation as reflected by their capacity to inhibit movements of Ca and to enhance intracellular levels of cyclic AMP.
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002449:Cell Aggregation / Q000187:drug effects; D003182:Complement C5 / Q000502:physiology; D000242:Cyclic AMP / Q000096:biosynthesis; D016861:Cyclooxygenase Inhibitors; D007213:Indomethacin / Q000494:pharmacology; D007975:Leukotriene B4 / Q000037:antagonists & inhibitors; D008213:Lymphocyte Activation / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010894:Piroxicam; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D012459:Salicylates / Q000494:pharmacology; D013481:Superoxides / Q000096:biosynthesis; D013843:Thiazines / Q000494:pharmacology; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors
D000893:Anti-Inflammatory Agents; D003182:Complement C5; D016861:Cyclooxygenase Inhibitors; D011448:Prostaglandin Antagonists; D012459:Salicylates; D013843:Thiazines; D013481:Superoxides; D010894:Piroxicam; D007975:Leukotriene B4; D013928:Thromboxane A2; D000242:Cyclic AMP; D001241:Aspirin; D002118:Calcium; D007213:Indomethacin