Chronic ethanol exposure changes dopamine D2 receptor splicing during retinoic acid-induced differentiation of human SH-SY5Y cells.
Journal Title: Pharmacological Reports - Year 2010, Vol 62, Issue 4
Abstract
There is evidence for ethanol-induced impairment of the dopaminergic system in the brain during development. The dopamine D2 receptor (DRD2) and the dopamine transporter (DAT) are decisively involved in dopaminergic signaling. Two splice variants of DRD2 are known, with the short one (DRD2s) representing the autoreceptor and the long one (DRD2l) the postsynaptic receptor. We searched for a model to investigate the impact of chronic ethanol exposure and withdrawal on the expression of these proteins during neuronal differentiation. RA-induced differentiation of human neuroblastoma SH-SY5Y cells seems to represent such a model. Our real-time RT-PCR, Western blot, and immunocytochemistry analyses of undifferentiated and RA-differentiated cells have demonstrated the enhanced expression of both splice variants of DRD2, with the short one being stronger enhanced than the long one under RA-treatment, and the DRD2 distribution on cell bodies and neurites under both conditions. In contrast, DAT was down-regulated by RA. The DAT is functional both in undifferentiated and RA-differentiated cells as demonstrated by [(3)H]dopamine uptake. Chronic ethanol exposure during differentiation for up to 4 weeks resulted in a delayed up-regulation of DRD2s. Ethanol withdrawal caused an increased expression of DRD2l and a normalization of DRD2s. Thus the DRD2s/DRD2l ratio was still disturbed. The dopamine level was increased by RA-differentiation compared to controls and was diminished under RA/ethanol treatment and ethanol withdrawal compared to RA-only treated cells. In conclusion, chronic ethanol exposure impairs differentiation-dependent adaptation of dopaminergic proteins, specifically of DRD2s. RA-differentiating SH-SY5Y cells are suited to study the impact of chronic ethanol exposure and withdrawal on expression of dopaminergic proteins during neuronal differentiation.
Authors and Affiliations
Catrin Wernicke, Julian Hellmann, Ulrich Finckh, Hans Rommelspacher
Keywords
Related Articles
- EP ID EP129329
- DOI -
- Views 120
- Downloads 0
Effects of the histamine H₃ receptor antagonist ABT-239 on cognition and nicotine-induced memory enhancement in mice.
The strong correlation between central histaminergic and cholinergic pathways on cognitive processes has been reported extensively. However, the role of histamine H(3) receptor mechanisms interacting with nicotinic mecha...
Restoration of immune system function is accelerated in immunocompromised mice by the B-cell-tropic isoxazole R-11.
Background: Restoration of impaired immune response in immunocompromised patients is a crucial problem. In this study we evaluated the efficacy of isoxazole R-11 in reconstitution of the immune response in immunosuppress...
Frequency-dependent inhibition of antidromic hippocampal compound action potentials by anti-convulsants.
Using rat hippocampal slices, extracellularly recorded antidromic compound action potentials (cAP) were produced in CA1 pyramidal cell populations by electrical stimulation of the alveus at 0.5 Hz. These responses were a...
Effect of blockage of the endocannabinoid system by CB(1) antagonism on cardiovascular risk.
The endocannabinoid system is a crucial player in the inflammatory processes underlying atherosclerosis. Recently, basic research studies and animal models have strongly supported the role of the endocannabinoid system n...
Introduction to early in vitro identification of metabolites of new chemical entities in drug discovery and development.
The introduction of combinatorial chemistry and robotics for high throughput screening has changed the way drugs are discovered today compared with 10-15 years ago when fewer compounds were tested in animal or organ mode...