Inhibition of thrombin-induced platelet aggregation by myristic acid.
Myristate inhibited thrombin-induced aggregation and production of diacylglycerols of rabbit platelets suspended in a modified Tyrode solution. The incorporation of inositol into platelet phospholipids in both steady and activated states was also inhibited by myristate. When platelets were incubated with 32P-inorganic phosphate in the presence of myristate, incorporation of the radioactivity into platelet phosphatidylinositols (PI) was distinctly inhibited, although that into phosphatidic acid (PA) was inhibited relatively little. These results suggest that thrombin-induced breakdown of inositol phospholipids and the metabolic pathway of PA to PI are inhibited by myristate. The saturated fatty acids which have lower and higher molecular weight than myristate revealed a little or no inhibitory effects on the aggregation and on these metabolic changes of platelet lipids, suggesting the specificity of chain-length in the inhibitory action. It is conceivable that the inhibition of thrombin-induced aggregation by myristate is associated with the inhibition of PI-turnover in the platelets treated with the fatty acid.
Fukamachi
N
N
Department of Physiological Chemistry, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
Watanabe
Y
Y
Kobayashi
B
B
D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D004075:Diglycerides / Q000096:biosynthesis; D005227:Fatty Acids / Q000494:pharmacology; D019814:Myristic Acid; D009227:Myristic Acids / Q000494:pharmacology*; D010712:Phosphatidic Acids / Q000097:blood; D010716:Phosphatidylinositols / Q000097:blood; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011817:Rabbits; D013917:Thrombin
D004075:Diglycerides; D005227:Fatty Acids; D009227:Myristic Acids; D010712:Phosphatidic Acids; D010716:Phosphatidylinositols; D010975:Platelet Aggregation Inhibitors; D019814:Myristic Acid; D013917:Thrombin