Summary
Earlier, we found that ε-aminocaproic acid (EACA) inhibited human platelet aggregation
induced by adenosine diphosphate (ADP) and collagen, but not aggregation by arachidonic
acid (AA). Since EACA is structurally similar to lysine, yet these two agents exhibit
vast difference in their antifibrinolytic activities, we chose to study the effect
of lysine on platelet aggregation. We used L-lysine-HCl in these studies because of
its high solubility in aqueous solutions while causing no change in pH when added
to human plasma. With lysine, we repeatedly found inhibition of ADP-, collagen- and
ristocetin-induced aggregation, but potentiation of AA-induced aggregation. Both the
inhibitory and potentiation effects were dose-dependent. Low doses of lysine inhibited
the secondary phase of aggregation; high doses of it also inhibited the primary phase
of aggregation. Potentiation of AA-induced aggregation was accompanied by increased
release of serotonin and formation of malondialdehyde. These effects were not confined
to human platelets; rat platelets were similarly affected. Platelets, exposed to lysine
and then washed and resuspended in an artificial medium not containing lysine, remained
hypersensitive to AA, but no longer showed decreased aggregation by collagen. Comparing
the effects of lysine with equimolar concentrations of sucrose, EACA, and α-amino-n-butyric
acid, we attribute the potent inhibitory effect of lysine to either the excess positive
charge or H+ and C1− ions. The -NH2 group on the α-carbon on lysine appears to be the determining factor for the potentiation
effect; the effect seems to be exerted on the cyclooxygenase level of AA metabolism.
Lysine and other chemicals with platelet-affecting properties similar to lysine may
be used as a tool for the study of the many aspects of a platelet aggregation reaction.
Keywords
Human and rat platelets - ε-Aminocaproic acid - α-Amino-n-butyric acid - Aspirin -
Imidazole
