Abstract
Membrane phospholipase D (PLD) is associated with numerous neuronal functions, such as axonal growth, synaptogenesis, formation of secretory vesicles, neurodegeneration, and apoptosis. PLD acts mainly on phosphatidylcholine, from which phosphatidic acid (PA) and choline are formed. In turn, PA is a key element of the PLD-dependent secondary messenger system. Changes in PLD activity are associated with the mechanism of action of olanzapine, an atypical antipsychotic. The aim of the present study was to assess the effect of short-term administration of the first-generation antipsychotic drugs haloperidol, chlorpromazine, and fluphenazine on membrane PLD activity in the rat brain. Animals were sacrificed for a time equal to the half-life of the antipsychotic drug in the brain, then the membranes in which PLD activity was determined were isolated from the tissue. The results indicate that only haloperidol in a higher dose increases the activity of phospholipase D. Such a mechanism of action of haloperidol has not been described previously. Induction of PLD activity by haloperidol may be related to its mechanism of cytotoxicity. The finding could justify the use of PLD inhibitors as protective drugs against the cytotoxicity of first-generation antipsychotic drugs like haloperidol.
Highlights
Phospholipase D (PLD) activity in carrot cells (EC 3.1.4.4.) was first described in 1947 [1]
Post hoc Tukey tests showed that FLU at a dose of 10 mmol/kg significantly reduced the PLD activity compared with the dose of 20 mmol/kg (p = 0.002), but not in comparison to the control group (p = 0.09)
Post hoc Tukey tests showed that HAL at a dose of 20 mmol/kg significantly increased membrane PLD activity in the rat brain in comparison with the control group (p = 0.009)
Summary
Phospholipase D (PLD) activity in carrot cells (EC 3.1.4.4.) was first described in 1947 [1]. Until the end of the 1970s, there was a belief that PLD was an enzyme found only in plants [1]. In 1979, Taki and Kanfer described the presence of olein-dependent PLD in rat brain tissue [2]. The discovery of PLD in mammals triggered an avalanche of research to determine the place of PLD in cell physiology and pathology. It is known that PLD is an enzyme present in all known mammalian cells except for some leukocytes [3,4]. PLD occurs in most cellular organelles: in the plasma membrane, the Golgi network, secretory vesicles, lysosomes, the nucleus, microsomes, and mitochondria. Low PLD activity was detected in cytoplasm [5]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
