Stimulation of the active transport of serotonin into human platelets by hydrogen peroxide.
The effect of H2O2 on the active transport of serotonin (5-HT) by human platelets was investigated. Platelets were exposed to either a single dose of H2O2 or to H2O2 generated by the glucose/glucose oxidase or xanthine/xanthine oxidase enzyme systems. H2O2 (12.5 to 100 microM) produced a rapid, concentration-dependent and time-dependent increase in 5-HT transport which was maximal after a 2-min incubation and decreased with continued incubation. Catalase (1000 units) completely prevented H2O2-induced stimulation, and fluoxetine (1 microM) totally blocked 5-HT uptake into stimulated platelets. The glucose/glucose oxidase (3.12 to 100 milliunits) and the xanthine/xanthine oxidase system, superoxide dismutase (250 units) failed to alter the stimulation, whereas catalase (1000 units) effectively prevented the response. The kinetics of 5-HT transport indicated that H2O2 treatment did not alter the Km of 5-HT transport (Km control = 1.0 +/- 0.2 x 10(-6) M vs Km H2O2 = 1.1 +/- 0.1 x 10(-6) M) but markedly increased the maximal rate of 5-HT transport (Vmax control = 131.4 +/- 4.6 pmol/10(8) platelets/4 min vs Vmax H2O2 = 206.7 +/- 9.1 pmol/10(8) platelets/4 min). These data demonstrated that exposure of human platelets to H2O2 resulted in a stimulation of the active transport of 5-HT and suggested that H2O2 may function to regulate this process.
Bosin
T R
TR
Pharmacology Section, Indiana University School of Medicine, Bloomington 47405.
D001693:Biological Transport, Active / Q000187:drug effects; D001792:Blood Platelets / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005609:Free Radicals; D005947:Glucose / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology*; D008560:Membrane Fluidity / Q000187:drug effects; D012701:Serotonin / Q000493:pharmacokinetics*; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology; D013268:Stimulation, Chemical
D005609:Free Radicals; D012701:Serotonin; D006861:Hydrogen Peroxide; D000254:Sodium-Potassium-Exchanging ATPase; D005947:Glucose