title: Activation of human platelet phospholipases C and A2 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 substituent 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 [Ca2+]i; diacylglycerol formation; phosphatidic acid accumulation, protein phosphorylations and arachidonate release. These agents activated both phospholipases C and A2. The trend of activating phospholipase C was triterpenes with two acetoxyl substituents > one acetoxyl/one hydroxyl substituents > two hydroxyl substituents. In activating phospholipase A2, triterpenes with two acetoxyl substituents were most effective, whereas the paired isomers with a hydroxyl group at C-15 alpha 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 A2.
authors.affiliation: Institute of Life Science, National Tsing Hua University, Hsinchu, Taiwan, ROC.
authors.forename: C N
authors.initials: CN
authors.lastname: Wang
authors.forename: J S
authors.initials: JS
authors.lastname: Chen
authors.forename: M S
authors.initials: MS
authors.lastname: Shiao
authors.forename: C T
authors.initials: CT
authors.lastname: Wang
mesh_terms: D016718:Arachidonic Acid / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology*; D004075:Diglycerides / Q000096:biosynthesis; D004789:Enzyme Activation; D006801:Humans; D010084:Oxidation-Reduction; D010100:Oxygen / Q000494:pharmacology; D010712:Phosphatidic Acids / Q000378:metabolism; D010741:Phospholipases A / Q000187:drug effects / Q000378:metabolism*; D054467:Phospholipases A2; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000494:pharmacology*; D010738:Type C Phospholipases / Q000187:drug effects / Q000378:metabolism*
chemical_list: D004075:Diglycerides; D010712:Phosphatidic Acids; D014315:Triterpenes; D016718:Arachidonic Acid; D010741:Phospholipases A; D054467:Phospholipases A2; D010738:Type C Phospholipases; D010100:Oxygen