A novel regulation of expression of the alpha-subunit of the G stimulatory protein by dopamine via D1 dopamine receptors.
Exposure of human neuroblastoma SK-N-MC cells to 100 microM dopamine (DA) for 72 h caused 70% loss of immunodetectable membrane-bound levels of the alpha-subunit of Ga. The loss in Gs alpha was accompanied by reduced (64.3 +/- 0.35% of control values) NaF-mediated stimulation of adenylyl cyclase and was independent of accumulated cyclic AMP (cAMP) levels, because neither forskolin nor dibutyryl cAMP treatment of cells mimicked the DA-induced effects. The reduction in Gs alpha content was manifest at the transcriptional level; Gs alpha mRNA levels were attenuated to 56.5 +/- 10% of control values after a 24-h treatment of cells with 100 microM DA. The concentration of DA required to produce the half-maximal decrease of Gs alpha mRNA content was 20 nM, similar to the high-affinity binding value (8.5 nM) of DA to D1 sites. Gs alpha mRNA levels were also attenuated (52 +/- 3.5% of control values) by the D1-selective agonist SKF R-38393 but not by forskolin or dibutyryl cAMP. Attenuation of Gs alpha mRNA levels by agonists was blocked by the D1-selective antagonist SCH 23390. Stimulation of adenylyl cyclase-inhibitory DA receptors, which are coexpressed in these cells, failed to down-regulate Gs alpha mRNA, indicating that regulation of Gs alpha mRNA expression occurs specifically through chronic stimulation of D1 DA receptors.
Sidhu
A
A
Department of Pediatrics, Georgetown University Medical Center, Georgetown University, Washington, D.C. 20007, USA.
Kimura
K
K
D015152:Blotting, Northern; D004298:Dopamine / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D012333:RNA, Messenger / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000502:physiology; D013997:Time Factors; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D019204:GTP-Binding Proteins; D004298:Dopamine