Inhibition of highly purified mammalian phospholipases A2 by non-steroidal anti-inflammatory agents. Modulation by calcium ions.
Highly purified Ca2+-dependent phospholipases A2 that were isolated from human platelets, rabbit alveolar macrophages and peritoneal polymorphonuclear leucocytes and were active in the neutral-to-alkaline pH range were inhibited 50% by 75 microM-indomethacin in the presence of 5.0 mM added Ca2+. Sodium meclofenamate and sodium flufenamate were also inhibitory; the sensitivity to inhibition was a function of Ca2+ concentration. The dose for 50% inhibition (ID50) with meclofenamate was 0.4 mM in the presence of 2.5 mM added Ca2+, but 50nM in the presence of 0.5 mM added Ca2+. Thus, inhibition of phospholipase A2 activity by non-steroidal anti-inflammatory agents via Ca2+ antagonism may significantly contribute to the mechanism of drug action.
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D005439:Flufenamic Acid / Q000494:pharmacology*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D008469:Meclofenamic Acid / Q000494:pharmacology*; D009504:Neutrophils / Q000201:enzymology; D010740:Phospholipases / Q000037:antagonists & inhibitors*; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D011817:Rabbits; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
D062367:ortho-Aminobenzoates; D008469:Meclofenamic Acid; D005439:Flufenamic Acid; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D002118:Calcium; D007213:Indomethacin