KINETIC AND PHARMACOLOGIC ANALYSIS OF 5-HYDROXYTRYPTAMINE TRANSPORT BY HUMAN PLATELETS AND PLATELET STORAGE GRANULES - COMPARISON WITH CENTRAL SEROTONERGIC NEURONS

Abstract

The mechanisms whereby human platelets transport serotonin (5-HT) were explored by determining initial velocity of 5-HT uptake over a wide range of 5HT 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 apparently were in error, and the correct kinetic constants were recalcualted. Saturable active uptake of 5-HT into human platelets was directly susceptible to inhibition by several pharmacologic agents (ouabain, metabolic inhibitors and tricyclic antidepressants) which did not inhibit nonsaturable passive diffusion nor the nonsaturable granular transport of 5-HT. Granular binding of 5-HT was directly susceptible to inhibition by pharmcologic agents (reserpine, tetrabenazien and N-ethylmaleimide) which did not directly inhibit saturable active uptake nor nonsaturable passive diffusion of 5-HT. Quantitative studies of platelet 5-HT transport showed that at low concentrations of 5-HT, 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, properties of 5-HT accumulation by platelets are determined mostly by the granular storage mechanism. Detailed comparisons of kinetic, biochemical and pharmacologic characteristics of 5-HT transport in platelets and brain support the notion that platelet can serve as a model for 5-HT transport by CNS neurons.