Increased inhibitory activity of protein kinase C on the serotonin transporter in OCD.
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 4beta-12-tetradecanoylphorbol 13-acetate (beta-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 beta-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.
Marazziti
D
D
Dipartimento di Psichiatria, Neurobiologia, Farmacologia e Biotecnologie, University of Pisa, Italy. dmarazzi@psico.med.unipi.it
Masala
I
I
Rossi
A
A
Hollander
E
E
Presta
S
S
Giannaccini
G
G
Mazzoni
M R
MR
Dell'Osso
L
L
Lucacchini
A
A
Cassano
G B
GB
D000293:Adolescent; D000328:Adult; D001692:Biological Transport / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002273:Carcinogens / Q000494:pharmacology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002648:Child; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009771:Obsessive-Compulsive Disorder / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D012701:Serotonin / Q000493:pharmacokinetics; D050486:Serotonin Plasma Membrane Transport Proteins; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D002273:Carcinogens; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate