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Different effects of five dopamine receptor subtypes on nuclear factor-kappaB activity in NG108-15 cells and mouse brain.
- Source :
-
Journal of neurochemistry [J Neurochem] 2004 Jan; Vol. 88 (1), pp. 41-50. - Publication Year :
- 2004
-
Abstract
- We previously showed that dopamine receptors D1R and D2R expressed in NG108-15 cells activated protein kinase A and extracellular signal-regulated kinase (ERK) respectively, resulting in differential activation of nuclear factor (NF)-kappaB activity. To investigate whether other dopamine receptor subtypes regulate NF-kappaB, we established NG108-15 cells stably expressing D3R, D4R and D5R (NGD3R, NGD4R and NGD5R). D5R stimulation with SKF 38393 decreased NF-kappaB luciferase reporter activity in NGD5R cells, similar to D1R stimulation in NGD1R cells. However, D3R or D4R stimulation with quinpirole showed no change in NF-kappaB-Luci activity, although forskolin-induced cyclic AMP responsive element-Luci activation was attenuated by quinpirole treatment in NGD2LR, NGD3R and NGD4R cells. As expected, activation of ERK or serum responsive element-luciferase reporter not observed following stimulation with quinpirole in D3R- or D4R-expressing cells. We further examined the effects of haloperidol and risperidone, which are typical and atypical antipsychotic drugs respectively, on NF-kappaB activity by gel shift assay in mouse frontal cortex. Haloperidol treatment slightly attenuated basal NF-kappaB activity. By contrast, risperidone treatment enhanced NF-kappaB activity. Taken together, D2R and D1R/D5R had opposite effects on NF-kappaB activity in NG108-15 cells. Risperidone up-regulated and haloperidol down-regulated NF-kappaB activity in mouse brain. This effect may be related to the atypical antipsychotic properties of risperidone.
- Subjects :
- Animals
Antipsychotic Agents pharmacology
Brain drug effects
Cell Line
Colforsin pharmacology
DNA metabolism
Dopamine Antagonists pharmacology
Electrophoretic Mobility Shift Assay
Frontal Lobe drug effects
Frontal Lobe metabolism
Gene Expression Regulation drug effects
Haloperidol pharmacology
Mice
Mitogen-Activated Protein Kinases drug effects
Mitogen-Activated Protein Kinases metabolism
Protein Binding drug effects
Rats
Receptors, Dopamine drug effects
Receptors, Dopamine genetics
Risperidone pharmacology
Brain metabolism
NF-kappa B metabolism
Receptors, Dopamine metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0022-3042
- Volume :
- 88
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of neurochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 14675148
- Full Text :
- https://doi.org/10.1046/j.1471-4159.2003.02129.x