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

24 Citations (Scopus)

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
StatePublished - 2000
Externally publishedYes

Fingerprint

Serotonin Plasma Membrane Transport Proteins
Obsessive-Compulsive Disorder
Protein Kinase C
Serotonin
Tetradecanoylphorbol Acetate
Phosphatidylinositols
Diagnostic and Statistical Manual of Mental Disorders
Healthy Volunteers
Enzymes

Keywords

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

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Neuroscience(all)
  • Psychology(all)

Cite this

Marazziti, D., Masala, I., Rossi, A., Hollander, E., Presta, S., Giannaccini, G., ... Cassano, G. B. (2000). Increased inhibitory activity of protein kinase C on the serotonin transporter in OCD. Neuropsychobiology, 41(4), 171-177.

Increased inhibitory activity of protein kinase C on the serotonin transporter in OCD. / Marazziti, Donatella; Masala, Irene; Rossi, Alessandra; Hollander, Eric; Presta, Silvio; Giannaccini, Gino; Mazzoni, Maria R.; Dell'Osso, Liliana; Lucacchini, Antonio; Cassano, Giovanni B.

In: Neuropsychobiology, Vol. 41, No. 4, 2000, p. 171-177.

Research output: Contribution to journalArticle

Marazziti, D, Masala, I, Rossi, A, Hollander, E, Presta, S, Giannaccini, G, Mazzoni, MR, Dell'Osso, L, Lucacchini, A & Cassano, GB 2000, 'Increased inhibitory activity of protein kinase C on the serotonin transporter in OCD', Neuropsychobiology, vol. 41, no. 4, pp. 171-177.
Marazziti D, Masala I, Rossi A, Hollander E, Presta S, Giannaccini G et al. Increased inhibitory activity of protein kinase C on the serotonin transporter in OCD. Neuropsychobiology. 2000;41(4):171-177.
Marazziti, Donatella ; Masala, Irene ; Rossi, Alessandra ; Hollander, Eric ; Presta, Silvio ; Giannaccini, Gino ; Mazzoni, Maria R. ; Dell'Osso, Liliana ; Lucacchini, Antonio ; Cassano, Giovanni B. / Increased inhibitory activity of protein kinase C on the serotonin transporter in OCD. In: Neuropsychobiology. 2000 ; Vol. 41, No. 4. pp. 171-177.
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