Activators of protein kinase C decrease serotonin transport in human platelets

Biochim Biophys Acta. 1992 Nov 17;1137(3):331-7. doi: 10.1016/0167-4889(92)90154-4.

Abstract

Treatment of human platelets with activators of protein kinase C (PKC) for 5-20 min resulted in substantial reductions in the rate of platelet serotonin (5-HT) transport. The mean Vmax observed after 5 min treatment with 1 microM 4-beta-12-tetradecanoylphorbol 13-acetate (beta-TPA) was 66% (n = 16, P = 0.0001) of the control value. 5 min of treatment with 1 microM mezerein reduced uptake to 78% (n = 3, P = 0.01) of control. Both beta-TPA and mezerein had little effect on the Km of transport and had EC50 values of approx. 100 mM when a 20-min treatment period was used. The maximum effects of both were reached at approx. 20 min and could be blocked with staurospine. The beta-TPA effect was stereospecific, as alpha-TPA did not alter platelet 5-HT uptake. Although the PKC activators may have altered transmembrane ion-gradients for Na+ and Cl-, which are co-transported with 5-HT, minimizing ion-gradient changes had little effect on the observed reductions in transport. The PKC activators also had little or no effect on platelet 5-HT release or on the number (Bmax) of 5-HT transporters expressed at the platelet surface. The data indicate that PKC activation may down-regulate the activity of the 5-HT transporter in platelets. Apparently, most of this effect is mediated through mechanisms other than changes in ion-gradients, reductions in the number of available transporters, or increased 5-HT release. The apparent regulation of 5-HT transport by PKC may have important implications in platelet and neuronal functioning.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alkaloids / pharmacology
  • Biological Transport
  • Blood Platelets / drug effects
  • Blood Platelets / metabolism*
  • Diterpenes*
  • Enzyme Activation
  • Humans
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / metabolism*
  • Serotonin / metabolism*
  • Staurosporine
  • Terpenes / pharmacology
  • Tetradecanoylphorbol Acetate / pharmacology

Substances

  • Alkaloids
  • Diterpenes
  • Terpenes
  • Serotonin
  • mezerein
  • Protein Kinase C
  • Staurosporine
  • Tetradecanoylphorbol Acetate