Department and Clinic of Psychiatry and Psychotherapy, Medical University of Silesia, Katowice, Poland.
Pharmacol Rep. 2013;65(3):724-9. doi: 10.1016/s1734-1140(13)71051-x.
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.
PLD activity was determined using a fluorometric assay. Ritanserin was used to determine the 5-HT receptor mode of action.
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%.
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.
磷脂酶 D (PLD) 在产生磷酸脂酸的第二信使系统中发挥关键作用，介导 5-羟色胺 5-HT2 受体活性等。本研究旨在评估非典型抗精神病药奥氮平 (OLZ) 和选择性 5-羟色胺再摄取抑制剂 (SSRI) 抗抑郁药帕罗西汀 (PX) 对大鼠大脑皮质分离的质膜中油酸盐激活的 PLD 活性的可能影响。
使用荧光测定法测定 PLD 活性。利坦色林用于确定 5-HT 受体作用模式。
单次给予 10 mmol/kg OLZ 对大鼠大脑皮质 PLD 活性没有改变，20 mmol/kg OLZ 引起的非显著性下降，而长期（21 天）给予 OLZ 导致 PLD 活性下降 41.9%。单次给予 PX 显著降低 PLD 活性：10 mmol/kg - 28.6%；20 mmol/kg - 31.5%，长期（21 天）给予 PX - 39.5%。
该研究表明，5-HT2 受体介导的油酸盐激活的 PLD 抑制可能是 OLZ 和 PX 作用机制的共同部分。
