CINATRINS, A NOVEL FAMILY OF PHOSPHOLIPASE A₂ INHIBITORS

II. BIOLOGICAL ACTIVITIES

Abstract

Cinatrins A, B and C₃ inhibited phospholipase A₂ purified from rat platelets in a dose-dependent manner. Cinatrin C₃, the most potent component (IC₅₀ 70μM), was noncompetitive with a Ki value of 36 μM. Cinatrins B and C₃ also inhibited both porcine pancreas and Naja naja venom phospholipase A₂. Inhibition of rat platelet phospholipase A₂ by cinatrin C₃ was independent of Ca²⁺ and substrate concentration. Comparison with duramycin, another phospholipase A₂ inhibitor, displayed inhibition dependent on substrate concentration when phosphatidylethanolamine was the substrate. These results indicate that the inhibition of phospholipase A₂ by cinatrin C₃ may result from direct interaction with the enzyme.