title: Differential regulation of NF-kappaB, SRE and CRE by dopamine D1 and D2 receptors in transfected NG108-15 cells.
abstract: To investigate transcriptional regulation by dopamine receptors, we established NG108-15 cells stably expressing D1R, D2LR and D2SR (NGD1R, NGD2LR and NGD2SR) and evaluated the effects of these receptors on NF-kappaB, SRE and CRE activity using luciferase reporter constructs. Stimulation with quinpirole, a selective D2R agonist, increased NF-kappaB and SRE activity but decreased CRE activity in both NGD2R cell lines. By contrast, stimulation with SKF 38393, a selective D1R agonist, decreased NF-kappaB and SRE activity but increased CRE activity in NGD1R cells. Stimulation with forskolin and overexpression of constitutively active PKA suppressed NF-kappaB activity, likely due to D1R stimulation. D2R stimulation activated ERK, and treatment with U1026, a selective MEK inhibitor, eliminated D2R-induced NF-kappaB activation. D2R stimulation also activated the neural cell adhesion molecule (NCAM) promoter, which includes a potential NF-kappaB site. Furthermore, by transfecting constitutively active CaM KII and MEKK, and dominant negative p38 MAPK, we show that the NCAM promoter is positively regulated by CaM KII but negatively regulated by p38 MAPK. These results indicate that D2R-induced NF-kappaB activation through ERK may be involved in activation of the NCAM promoter, and additionally that other protein kinases such as CaM KII and p38 MAPK also regulate NCAM expression.
authors.affiliation: Department of Pharmacology, Kumamoto University School of Medicine, Kumamoto, Japan. yusuket@gpo.kumamoto-u.ac.jp
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Takeuchi
authors.forename: Kohji
authors.initials: K
authors.lastname: Fukunaga
mesh_terms: D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism; D002999:Clone Cells; D005576:Colforsin / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D017930:Genes, Reporter; D006822:Hybrid Cells; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D019006:Neural Cell Adhesion Molecules / Q000235:genetics; D009447:Neuroblastoma / Q000378:metabolism; D011401:Promoter Regions, Genetic; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D020218:Response Elements / Q000235:genetics / Q000502:physiology*; D027602:Serum Response Element / Q000235:genetics / Q000502:physiology; D014162:Transfection; D014407:Tumor Cells, Cultured; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D018491:Dopamine Agonists; D004791:Enzyme Inhibitors; D016328:NF-kappa B; D019006:Neural Cell Adhesion Molecules; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C113776:dopamine D2L receptor; D005576:Colforsin; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases