Activation of human platelet phospholipases C and A 2 by various oxygenated triterpenes

Abstract

Eight structural analogues of oxygenated triterpenes exerted striking differences in activation of human platelets. They are four pairs of stereoisomers and two pairs of positional isomers with varying: 1) acetoxyl / hydroxyl substituents; 2) the position of the substituents at C-3 and C-15; and 3) the stereochemistry of a substituents at C-3. It required a threshold concentration for each agent to cause the concentration-dependent activation. These triterpenes were hydrophobic with <20% difference in the partition coefficients between 1-octanol and water. They caused differential effects on: inositol triphosphate production; the increase in [Ca 2+] i; diacylglycerol formation; phosphatidic acid accumulation, protein phosphorylations and arachidonate release. These agents activated both phospholipases C and A 2. The trend of activating phospholipase C was triterpenes with two acetoxyl substituents > one acetoxyl/one hydroxyl substituents > two hydroxyl substituents. In activating phospholipase A 2, triterpenes with two acetoxyl substituents were most effective, whereas the paired isomers with a hydroxyl group at C-15α and an acetoxyl substituent at C-3 failed the activation. The results enable one to discuss the possible structure-activity relationship of various oxygenated triterpenes in the activation of both phospholipases C and A 2.