Biological activity of platelet activating factor-amidophosphonate (PAF-AP), a novel phosphonolipid selective inhibitor of platelet activating factor (PAF).
A novel amidophosphonate analog of Platelet Activating Factor (PAF), trimethyl (3-phosphonopropyl) ammonium hydroxide (R)-mono[2-acetamido-3-(hexadecyloxy)propyl] ester (PAF-AP), was synthesized. A potent inhibitor of aggregation induced by Platelet Activating Factor, arachidonic acid, Ca2+-ionophore, ADP, and thrombin, PAF-AP had no or very little effect on aggregation induced by epinephrine and collagen. Inhibition of phospholipase A2 and C2 activity was suggested from suppression of release of [14C]-arachidonic acid from pre-labeled platelet glycerophospholipids.
D000244:Adenosine Diphosphate / Q000037:antagonists & inhibitors; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000037:antagonists & inhibitors / Q000097:blood; D001792:Blood Platelets / Q000378:metabolism; D000001:Calcimycin / Q000037:antagonists & inhibitors; D003094:Collagen / Q000037:antagonists & inhibitors; D004075:Diglycerides / Q000096:biosynthesis; D004837:Epinephrine / Q000494:pharmacology; D006801:Humans; D010084:Oxidation-Reduction; D010712:Phosphatidic Acids / Q000096:biosynthesis; D010972:Platelet Activating Factor / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology / Q000502:physiology; D010974:Platelet Aggregation / Q000187:drug effects*; D013917:Thrombin / Q000037:antagonists & inhibitors
D001095:Arachidonic Acids; D004075:Diglycerides; D010712:Phosphatidic Acids; D010972:Platelet Activating Factor; C047125:platelet activating factor-amidophosphonate; D016718:Arachidonic Acid; D000001:Calcimycin; D000244:Adenosine Diphosphate; D003094:Collagen; D013917:Thrombin; D004837:Epinephrine