Effects of olanzapine and paroxetine on phospholipase D activity in the rat brain.
BACKGROUND
Phospholipase D (PLD) plays a key role in a second messenger system producing phosphatidic acid, mediating, among others, serotonin 5-HT2 receptor activity. The aim of the study was to evaluate a possible effect of atypical antipsychotic drug, olanzapine (OLZ), and selective serotonin reuptake inhibitor (SSRI) antidepressant, paroxetine (PX), on oleate-activated PLD activity in plasma membranes isolated from rat brain cortex.


METHODS
PLD activity was determined using a fluorometric assay. Ritanserin was used to determine the 5-HT receptor mode of action.


RESULTS
A single dose of 10 mmol/kg OLZ produced no change in rat brain cortex PLD activity, 20 mmol/kg OLZ caused a nonsignificant decrease, and long-term (21 days) administration of OLZ resulted in a 41.9% decrease in PLD activity. Single doses of PX significantly decreased PLD activity: 10 mmol/kg - by 28.6%; 20 mmol/kg - by 31.5%, and long-term (21 days) administration of PX - by 39.5%.


CONCLUSIONS
The study indicates that the 5-HT2 receptor-mediated inhibition of oleate-activated PLD may be a common part of the mechanisms of action of OLZ and PX.
Department and Clinic of Psychiatry and Psychotherapy, Medical University of Silesia, Katowice, Poland. krzystanekmarek@gmail.com
Marek
M
Krzystanek
Ewa
E
Krzystanek
Henryk I
HI
Trzeciak
Andrzej
A
Małecki
Irena
I
Krupka-Matuszczyk
Małgorzata
M
Janas-Kozik
Janusz K
JK
Rybakowski
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D014150:Antipsychotic Agents / Q000494:pharmacology; D001569:Benzodiazepines / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D008297:Male; D000077152:Olanzapine; D017374:Paroxetine / Q000494:pharmacology*; D010739:Phospholipase D / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D044348:Receptors, Serotonin, 5-HT2 / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology
D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D001569:Benzodiazepines; D000077152:Olanzapine; D017374:Paroxetine; D010739:Phospholipase D; D044348:Receptors, Serotonin, 5-HT2; D017367:Selective Serotonin Reuptake Inhibitors