Activation of rabbit platelet phospholipase and thromboxane synthesis by 1-O-hexadecyl/octadecyl-2-acetyl-sn-glyceryl-3-phosphorylcholine (platelet activating factor).
1-O-Hexadecyl/octadecyl-2-acetyl-sn-glyceryl-3-phosphorylcholine (AGEPC), structurally identical with platelet activating factor, is a potent stimulus for rabbit platelet aggregation and serotonin secretion. AGEPC at concentrations between 10(-10) and 10(-8) M induced stimulation of rabbit platelet synthesis of thromboxane B2. The dose vs. response curve for platelet thromboxane B2 synthesis was displaced slightly towards higher stimulus concentrations compared to [3H]serotonin secretion, with half-maximal concentrations of 2.5 . 10(-9) and 8 . 10(-10) M, respectively. Rates of thromboxane B2 synthesis and secretion were similar with a t 1/2 max of 4.0-4.5 s for both processes. AGEPC induced a decrease in platelet [14C]arachidonic acid in both phosphatidylinositol and phosphatidylcholine, although [14C]arachidonic acid turnover in phosphatidylcholine was not observed below 1 . 10(-8) M AGEPC. Concomitantly, this decrease in phospholipid [14C]arachidonic acid was associated with a marked increase of radiolabel in platelet diacylglycerol and phosphatidic acid 15 s after AGEPC addition, suggesting the possibility of a phospholipase C-diacylglycerol lipase mechanism of fatty acid cleavage. As observed previously with secretion and aggregation, removal of the 2-acetyl group from AGEPC abrogated all capacity of this molecule to stimulate platelet phospholipase. This study indicates that AGEPC (or platelet activating factor) activation of rabbit platelet phospholipase occurs in a time-course and concentration range similar to that required for [3H]serotonin secretion.
D000818:Animals; D001095:Arachidonic Acids / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005989:Glycerides / Q000097:blood; D007700:Kinetics; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D010740:Phospholipases / Q000097:blood*; D010743:Phospholipids / Q000097:blood; D010972:Platelet Activating Factor; D011817:Rabbits; D012701:Serotonin / Q000378:metabolism; D013929:Thromboxane B2 / Q000096:biosynthesis*; D013931:Thromboxanes / Q000096:biosynthesis*
D001095:Arachidonic Acids; D005989:Glycerides; D008244:Lysophosphatidylcholines; D010743:Phospholipids; D010972:Platelet Activating Factor; D013931:Thromboxanes; D012701:Serotonin; D013929:Thromboxane B2; D010740:Phospholipases