Defective serotonin transport mechanism in platelets from endogenously depressed patients.
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Biomedical subjects
Publications and source records attributed to R Malmgren.
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The 5-HT uptake mechanism in human platelets was studied in undiluted platelet-rich plasma (PRP). The kinetic data obtained, which were based on 5-HT concentrations ranging from 0.17 to 1.7 mumol/l, were analyzed according to Lineweaver-Burk, Eadie-Hofstee, Scatchard and Sips. In undiluted PRP all the analyses revealed a strict linearity between 5-HT concentrations and initial uptake velocities. Only one site for active transport seemed to be involved and no passive diffusion was present. The apparent Km and Vmax in a 95 per cent confidence interval (n = 25) were 1.20 +/- 0.14 mumol/l and 1.40 +/- 0.15 pmol/10(6) platelets and minutes, respectively. Dilution of PRP with autologous platelet-poor plasma or Ringer's solution markedly influenced the active 5-HT transport mechanism. The addition of minute amounts of supernatant from lysed autologous platelets to PRP totally impaired the active 5-HT uptake. It is concluded that relevant studies on the active 5-HT transport can be performed only in fresh undiluted PRP. The commonly used Lineweaver-Burk analysis does not discriminate sufficiently between fully saturable and non-saturable transport mechanism and therefore cannot be used for the detection of irregularities in the 5-HT transport.
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Heparinized human blood containing platelets labelled with 14C-serotonin and 51Cr was exposed to a polyethylene surface by rotation in Chandler loops. Both uptake of platelets on the surface and platelet aggregation in the blood occurred. More 14C- than 51Cr activity accumulated on the surface. It was demonstrated that this was due to an active uptake of 14C-serotonin by the surface-adherent platelets, which also retained their capacity to exert a release reaction.
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