Evidence for the existence of high affinity binding sites for indomethacin on human blood platelets.
Using human blood-washed platelets and [3H]indomethacin, we demonstrated the presence of saturable, time- and temperature-dependent high affinity binding sites for non-steroidal anti-inflammatory drugs. The observed Kd value for indomethacin was 5 nM. Structural specificity of the non-steroidal anti-inflammatory drug site was studied with arylacetic acids, anthranilic acids, and compounds from other chemical families. Arylacetic acid drugs had affinities which were similar to the affinity of indomethacin. Affinity differences among the other drugs may be related to the presence or absence of the lipophilic substituent on the central ring. As expected, anti-inflammatory pyrrazole derivatives, aspirin, bucloxic acid, cortisol, nordihydroguaiaretic acid, and the chemotactic peptide formyl-Met-Leu-Phe were not recognized by the indomethacin binding site.
D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001665:Binding Sites; D001667:Binding, Competitive; D001792:Blood Platelets / Q000032:analysis*; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000097:blood*; D008968:Molecular Conformation; D011955:Receptors, Drug / Q000032:analysis*; D013329:Structure-Activity Relationship; D014316:Tritium
D000893:Anti-Inflammatory Agents; D011955:Receptors, Drug; D014316:Tritium; D007213:Indomethacin