Methamphetamine Regulation of Sulfotransferases in Rat Liver and Brain

Abstract

Problem statement: Sulfotransferases (SULTs) are important phase II drug metabolizing enzymes. They also regulate the biological activities of various hormones. To the best of our knowledge, psychostimulants regulation of SULTs is basically not studied except one article reported that Methamphetamine (METH) treatment induced rat amygdale rSULT1A1 mRNA 4.3 fold by using microarray method to identify a series of candidate genes after single-dose METH treatment. The psychostimulant METH is used to treat disorders such as attention deficit, narcolepsy and obesity. It is also a highly addictive drug that causes serious social problems. The abuse of this drug leads to the damage of monoaminergic systems in the mammalian brain. It is important to understand how SULT expressions are regulated by psychostimulants. Approach: This study was performed to evaluate the effect of METH on SULT gene expressions in rat liver and brain. METH (0, 1, 5, 20 mg kg −1 day −1 ) was used to treat male and female rats for 7 days by oral administration. Rat livers and brains were collected 24 h after the final drug treatment. Western blot and real-time RT-PCR were used to investigate the effect of METH on SULT protein and mRNA expression, respectively, in rat liver and brain. Results: Proteins and mRNAs of rSULT1A1, rSULT2A1 and rSULT1E1 were induced in liver and brain of both male and female rats following METH treatment. rSULT1E1 was induced at much higher level compared to that of rSULT1A1 and rSULT2A1. Brain inductions were found to be much higher than those found in liver. Conclusion: These data suggest an important role of the central dopaminergic system in the regulation of liver and brain rSULT expressions.

Exogenous dopamine induces dehydroepiandrosterone sulfotransferase (rSULT2A1) in rat liver and changes the pharmacokinetic profile of moxifloxacin in rats

“…In this study, the strength of rSULT2A1 induction by DA in rat liver was in agreement with that from in vitro study. Besides, it was demonstrated that methamphetamine, a structural analogue of DA, could induce the protein expressions of rSULT2A1 less than 2-fold, but with statistical significance, in rat liver, [24] which is consistent to our results as well.…”

“…One recent paper demonstrated that SULT1A3 could be induced by DA in vitro, indicating the role of SULT1A3 in CNS by protecting neuronal cells from DA toxicity [25]. Besides, our previous results showed that methamphetamine, a structural analogue of DA, could induce the expressions of rSULT2A1 remarkably in rat liver and brain [23,24]. Our recent data in vitro also revealed that the activity of SULT2A1 in HepG2 cells increased significantly after the treatment with DA, and the expression of SULT2A1 was significantly induced by specific D1 agonists (SKF-38393 and SKF 82958) that activating D1 signaling pathway selectively [26].…”

Methamphetamine regulation of sulfotransferase 1A1 and 2A1 expression in rat brain sections

“…This report showed that the treatment induced rat brain rSULT1A1 mRNA 4.3-fold in the amygdale. Later, our results indicated that METH induced rSULT1A1, rSULT2A1 and rSULT1E1 protein expression both in the rat liver and brain (Zhou et al, 2010). In this study, the effect of short- and long-term treatment of male rats with METH on rSULT1A1 and rSULT2A1 expressions in the cerebellum, frontal cortex, hippocampus, and striatum was studied.…”

Caffeine induction of sulfotransferases in rat liver and intestine

“…Our previous results indicate that the anti‐cancer drug methotrexate (Maiti and Chen, ; Chen et al , , , ; Dutta et al , ) and all‐ trans ‐retinoic acids (Maiti et al , ) show induction activities toward various human and rat SULTs. Isoflavones (Chen et al , , ) and methamphetamine (Zhou et al , ) have also been shown to regulate rat SULTs expression.…”