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

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-tetranecanoylphorbol-13-acetate (P-TPA) on the platelet 5-HT uptake of young and elderly subjects, through the measurement of the 5-HT uptake itself and H-3-paroxetine ([H-3]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 [H-3]PAR binding was performed following the Marazziti et al method. Results: The results showed that P-TPA reduced significantly the maximal velocity (Vmax) of 5-HT uptake, with no change in the Michaelis constant or in [H-3]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 [H-3]PAR binding sites. The responsiveness of this pathway is identical in both young and elderly subjects. (C) 1999 Society of Biological Psychiatry.