Increased inhibitory activity of protein kinase C on the serotonin transporter in OCD

Donatella Marazziti, Irene Masala, Alessandra Rossi, Eric Hollander, Silvio Presta, Gino Giannaccini, Maria R. Mazzoni, Liliana Dell'Osso, Antonio Lucacchini, Giovanni B. Cassano

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Different observations show a reduced functionality of the serotonin (5-HT) transporter in obsessive-compulsive disorder (OCD) that might be due to a disturbance of its regulation at intracellular level. Protein kinase C (PKC) has been reported to provoke a decrease in the number of the 5-HT transporter proteins. Therefore, we investigated whether OCD patients differed from control subjects in the effect of PKC upon the 5-HT transporter, after stimulation of this enzyme with 4β-12-tetradecanoylphorbol 13-acetate (β-TPA). Fifteen patients affected by OCD, according to DSM-IV criteria, were compared with a similar group of healthy subjects. The determination of 5-HT uptake was carried out according to the method of Arora and Meltzer with slight modifications. At baseline, OCD patients showed a significant decrease in the maximal velocity (V(max)) of 5-HT uptake, as compared with control subjects, with no change in the Michaelis-Menten constant (K(m)). The activation of PKC with β-TPA provoked a significant decrease in V(max) values in both groups, but the effect was significantly more robust in OCD patients who, in turn, also showed also an increase in K(m) values. These findings could indicate the presence of hyperactivity of PKC in OCD that could be the result of increased activity of the phosphatidylinositol pathway. In addition, this suggests new potential therapeutic targets in OCD. Copyright (C) 2000 S. Karger AG, Basel.

Original languageEnglish (US)
Pages (from-to)171-177
Number of pages7
JournalNeuropsychobiology
Volume41
Issue number4
DOIs
StatePublished - Jan 1 2000
Externally publishedYes

Keywords

  • Obsessive-compulsive disorder
  • Phosphatidylinositol pathway
  • Protein kinase of type C
  • Protein kinase type C activators
  • Serotonin
  • Serotonin transporter

ASJC Scopus subject areas

  • Neuropsychology and Physiological Psychology
  • Psychiatry and Mental health
  • Biological Psychiatry

Fingerprint Dive into the research topics of 'Increased inhibitory activity of protein kinase C on the serotonin transporter in OCD'. Together they form a unique fingerprint.

  • Cite this

    Marazziti, D., Masala, I., Rossi, A., Hollander, E., Presta, S., Giannaccini, G., Mazzoni, M. R., Dell'Osso, L., Lucacchini, A., & Cassano, G. B. (2000). Increased inhibitory activity of protein kinase C on the serotonin transporter in OCD. Neuropsychobiology, 41(4), 171-177. https://doi.org/10.1159/000026656