Inhibitory effects of long-chain alkyltrimethylammonium ions on aggregation of bovine platelets and the relation of their effects to Ca2+ mobilization.
The inhibitory effects 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 effects on ADP-induced aggregation and their alkyl chain lengths from C8 to C18 was investigated. Results showed that the inhibitory effects of ammonium cations increased with increase of their alkyl chain lengths up to C16, and that the increase was linear with chain lengths of up to C14. 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 Ca2+ both in the presence and absence of extracellular Ca2+. These results suggest that inhibition of platelet aggregation by alkyltrimethylammonium ions is mainly due to their inhibition of increase in cytoplasmic Ca2+ by inhibition of both intracellular Ca2+ mobilization and Ca2+ uptake.
Kitagawa
S
S
Faculty of Pharmaceutical Sciences, University of Tokushima, Japan.
Ishida
M
M
Kotani
K
K
Kametani
F
F
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002417:Cattle; D003600:Cytosol / Q000378:metabolism; D008560:Membrane Fluidity / Q000187:drug effects; D008970:Molecular Weight; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D013917:Thrombin / Q000494:pharmacology
D010975:Platelet Aggregation Inhibitors; D000644:Quaternary Ammonium Compounds; D000244:Adenosine Diphosphate; D013917:Thrombin; D002118:Calcium