Effect of carbamazepine on expression of UDP-glucuronosyltransferase 1A6 and 1A7 in rat brain

Abstract

Because UDP-glucuronosyltransferase (Ugt) 1a6 and Ugt1a7 are highly expressed in the rat brain, changes in Ugt1a6 and Ugt1a7 expression may affect the pharmacokinetics of drugs and endogenous compounds in the brain. The present study aimed to elucidate the effect of carbamazepine (CBZ), a typical UGT inducer, on Ugt1a6 and Ugt1a7 expression in the rat brain. Sprague-Dawley rats were treated intraperitoneally for 7 d with CBZ (100 mg/kg/d). Ugt1a6 and Ugt1a7 mRNAs were induced by CBZ in the cerebellum, piriform cortex, and hippocampus (Ugt1a6: 3.1-, 2.4-, and 1.9-fold, respectively, Ugt1a7: 2.3-, 1.6-, and 3.1-fold, respectively); serotonin glucuronidation, which is catalyzed by Ugt1a6, was also increased by 2.8-, 1.7-, and 1.8-fold in these regions, respectively. The nuclear translocation of the constitutive androstane receptor was increased 1.4-fold in the cerebellum and piriform cortex, suggesting that brain Ugt1a6 and Ugt1a7 might be induced via the constitutive androstane receptor. However, the pregnane X receptor and nuclear factor erythroid 2-related factor 2 did not play decisive roles in the induction. Histone H3 lysine 9 acetylation, H3 lysine 4 pan-methylation, and H3 lysine 9 mono-methylation may not be required for the induction. This study clarified that CBZ affected Ugt1a6 and Ugt1a7 in the brain.