Abstract

The mechanisms whereby human platelets transport serotonin (5-HT) were explored by determining the initial velocity of 5-HT uptake over a wide range of 5-HT concentrations. Total 5-HT transport could be resolved into a saturable high affinity-low capacity active transport system plus nonsaturable passive diffusion. Previous kinetic analyses of 5-HT transport into platelets and brain slices have been found to be in error and the correct kinetic constants have been recalculated here. The saturable active uptake of 5-HT into human platelets is directly susceptible to inhibition by several pharmacologic agents (ouabain, metabolic inhibitors and tricyclic antidepressants) which do not inhibit the nonsaturable passive diffusion nor the nonsaturable granular transport of 5-HT. On the other hand, granular binding of 5-HT is directly susceptible to inhibition by pharmacologic agents (reserpine, tetrabenazine and N-ethylmaleimide) which do not directly inhibit saturable active uptake nor nonsaturable passive diffusion of 5-HT. Quantitative studies of platelet 5-HT transport have shown that at low concentrations of 5-HT, the pharmacologic and biochemical properties of total 5-HT transport are determined mostly by the saturable high affinity active membrane transport system for 5-HT; at high concentrations of 5-HT, the properties of 5-HT accumulation by platelets are determined mostly by the granular storage mechanism. Detailed comparisons of the kinetic, biochemical and pharmacologic characteristics of 5-HT transport in platelets and brain support the notion that the platelet can serve as a model for 5-HT transport by central nervous system neurons.