Modes of Action of Aspirin-Like Drugs

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 82; no. 21; pp. 7227 - 7231
• Main Authors: Abramson, Steven, Korchak, Helen, Ludewig, Rocio, Edelson, Henry, Haines, Kathleen, Levin, Richard I., Herman, Robert, Rider, Lisa, Kimmel, Steven, Weissmann, Gerald
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01.11.1985; National Acad Sciences
• Subjects: Aggregation; Anti-Inflammatory Agents - pharmacology; Aspirin - pharmacology; Biological and medical sciences; Blood Platelets - drug effects; Bones, joints and connective tissue. Antiinflammatory agents; Calcium; Calcium - metabolism; Cell Aggregation - drug effects; Complement C5 - physiology; Cyclic AMP - biosynthesis; Cyclooxygenase Inhibitors; Fluorescence; Indomethacin - pharmacology; Leukotriene B4 - antagonists & inhibitors; Lymphocyte Activation - drug effects; Medical sciences; Neutrophil activation; Neutrophils; Neutrophils - drug effects; Neutrophils - metabolism; Pharmacology. Drug treatments; Piroxicam; Platelets; Prostaglandin Antagonists - pharmacology; Prostaglandins; Salicylates; Salicylates - pharmacology; Sodium; Superoxides - biosynthesis; Thiazines - pharmacology; Thromboxane A2 - antagonists & inhibitors; Thromboxanes; Non steroidal antiinflammatory agent; Human; Calcium; Neutrophile; Ion transport; AMP-3',5'; Activation; Ratio; Inhibition; Intracellular; Mechanism of action; Divalent cation
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.82.21.7227

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.