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Dehydroepiandrosterone sulfotransferase (SULT2A1) plays an important role in the detoxification of hydroxyl-containing xenobitotics and in the regulation of the biological activities of hydroxysteroids.Ahhough dopamine (DA) is a vital neurotransmitter, DA also has some special functions in outer peripheral system and takes effect by binding with dopamine receptors including five subtypes (D1-D5).The objective of this study was to investigate the role of D1 subtype dopamine receptors (DRD1) in the regulation of SULT2A1 in HepG2 cells and in rat liver.All the 5 DR subtypes (D1-D5) were found to be expressed both in vitro and in vivo.Treatment of HepG2 cells with the specific D1 agonists SKF82958 or SKF38393 signifiantly increased the mRNA and protein expression of both D1 and SULT2A1, and increased SULT2A1 activity and cAMP levels.These effects were partially blocked by co-treatment with the specific D1 antagonist SCH23390.In addition, transfection of HepG2 cells with D1-specific siRNAs decreased D1 mRNA expression, which resulted in the reduction of SULT2A1 expression and enzyme activity significantly.