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Different effects of five dopamine receptor subtypes on nuclear factor‐κB activity in NG108‐15 cells and mouse brain
Author(s) -
Takeuchi Yusuke,
Fukunaga Kohji
Publication year - 2004
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2003.02129.x
Subject(s) - quinpirole , haloperidol , dopamine receptor d2 , endocrinology , medicine , dopamine receptor , stimulation , dopamine , chemistry , mapk/erk pathway , dopaminergic , apomorphine , signal transduction , biology , biochemistry
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)‐κB activity. To investigate whether other dopamine receptor subtypes regulate NF‐κB, we established NG108‐15 cells stably expressing D3R, D4R and D5R (NGD3R, NGD4R and NGD5R). D5R stimulation with SKF 38393 decreased NF‐κB 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‐κB‐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‐κB activity by gel shift assay in mouse frontal cortex. Haloperidol treatment slightly attenuated basal NF‐κB activity. By contrast, risperidone treatment enhanced NF‐κB activity. Taken together, D2R and D1R/D5R had opposite effects on NF‐κB activity in NG108‐15 cells. Risperidone up‐regulated and haloperidol down‐regulated NF‐κB activity in mouse brain. This effect may be related to the atypical antipsychotic properties of risperidone.