Regulation of the platelet serotonin transporter by protein kinase C in the young and elderly

Biol Psychiatry. 1999 Feb 15;45(4):443-7. doi: 10.1016/s0006-3223(98)00055-9.

Abstract

Background: Some data show that different factors may influence the serotonin (5-HT) uptake rate. Our study aimed at evaluating the possible role of a protein kinase C (PKC) activator, i.e., 4-beta-12-tetradecanoylphorbol-13-acetate (beta-TPA) on the platelet 5-HT uptake of young and elderly subjects, through the measurement of the 5-HT uptake itself and 3H-paroxetine ([3H]PAR) binding sites, which correspond to the transporter protein.

Methods: Human platelets and 5-HT uptake were evaluated according to the method of Arora and Meltzer, while [3H]PAR binding was performed following the Marazziti et al method.

Results: The results showed that beta-TPA reduced significantly the maximal velocity (Vmax) of 5-HT uptake, with no change in the Michaelis constant or in [3H]PAR binding parameters, in platelets of both young and elderly subjects. Although this last group of subjects had a significantly lower Vmax than the other, the degree of inhibition was almost the same (75%) in both.

Conclusions: These findings indicate that PKC decreases the 5-HT uptake rate by modifying the phosphorylation state of the transporter and with no change in the number of [3H]PAR binding sites. The responsiveness of this pathway is identical in both young and elderly subjects.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aging / physiology*
  • Binding Sites
  • Blood Platelets / drug effects*
  • Blood Platelets / metabolism
  • Carrier Proteins / drug effects*
  • Carrier Proteins / metabolism
  • Enzyme Activation / drug effects
  • Enzyme Activation / physiology
  • Female
  • Humans
  • Male
  • Membrane Glycoproteins / drug effects*
  • Membrane Glycoproteins / metabolism
  • Membrane Transport Proteins*
  • Nerve Tissue Proteins*
  • Paroxetine / metabolism
  • Protein Kinase C / drug effects*
  • Protein Kinase C / physiology
  • Selective Serotonin Reuptake Inhibitors / metabolism
  • Serotonin / metabolism
  • Serotonin / pharmacokinetics*
  • Serotonin Plasma Membrane Transport Proteins
  • Tetradecanoylphorbol Acetate / pharmacology*

Substances

  • Carrier Proteins
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin Uptake Inhibitors
  • Serotonin
  • Paroxetine
  • Protein Kinase C
  • Tetradecanoylphorbol Acetate