Different effects of five dopamine receptor subtypes on nuclear factor-kappaB activity in NG108-15 cells and mouse...

Area of Science:

• Neuroscience
• Molecular Biology
• Pharmacology

Background:

• Dopamine receptors (DRs) modulate intracellular signaling pathways.
• Previous studies indicated dopamine receptors D1R and D2R differentially regulate nuclear factor-kappaB (NF-κB) activity.
• The role of other dopamine receptor subtypes (D3R, D4R, D5R) in NF-κB regulation remained unclear.

Purpose of the Study:

• To investigate the effects of dopamine receptor subtypes D3R, D4R, and D5R on NF-κB activity.
• To examine the impact of antipsychotic drugs (haloperidol and risperidone) on NF-κB activity in the mouse frontal cortex.

Main Methods:

• Established NG108-15 cell lines stably expressing D3R, D4R, and D5R.
• Utilized luciferase reporter assays to measure NF-κB activity following receptor stimulation.
• Assessed cyclic AMP responsive element and serum-responsive element-luciferase reporter activity.
• Employed gel shift assays to analyze NF-κB activity in mouse frontal cortex tissue.

Main Results:

• Dopamine receptor D5R stimulation decreased NF-κB luciferase reporter activity, similar to D1R.
• Dopamine receptors D3R and D4R stimulation did not alter NF-κB activity but attenuated forskolin-induced cyclic AMP responsive element activation.
• Haloperidol slightly reduced basal NF-κB activity, whereas risperidone enhanced it in mouse frontal cortex.

Conclusions:

• Dopamine receptors D1R and D5R exhibit opposing effects on NF-κB activity compared to D2R in NG108-15 cells.
• Risperidone up-regulates and haloperidol down-regulates NF-κB activity in the mouse brain.
• These findings suggest a potential mechanism for the atypical antipsychotic properties of risperidone related to NF-κB modulation.