Inhibitory effects of long-chain alkyltrimethylammonium ions on aggregation of bovine platelets and the relation of their effects to Ca 2+ mobilization

Abstract

The inhibitory efefcts of alkyltrimethylammonium ions on ADP-and thrombin-induced aggregation of bovine platelets were investigated. The ammonium cations inhibited the two aggregation reactions to similar extents. The relationship between their inhibitory efects on ADP-induced aggregation and their alkyl chain lengths from C 8 to C 18 was investigated. Results showed that the inhibitory effects of ammonium cations increased with increase of their alkyl chain lengths up to C 16, and that the increase was linear with chain lengths of up to C 14. This linear relation and slope of the linear regression line suggested that the inhibitory effects of the ammonium cations depended on their partitioning into the membrane. However, unlike long-chain unsaturated fatty acids, they did not affect the membrane fluidity of the platelets, Fluorescence analysis of fura-2 loaded platelets revealed that, in the concentration range where the alkyltrimethylammonium ions inhibited aggregation, they inhibited agonist-induced increase in cytosolic Ca 2+ both in the presence and absence of extracellular Ca 2+. These results suggest that inhibition of platelet aggregation by alkyltrimethylammonium ionsis mainly due to their inhibition of increase in cytoplasmic Ca 2+ by inhibition of both intracellular Ca + mobilization and Ca 2+ uptake.