Benzo(alpha)pyrene-induced up-regulation of CYP1A2 gene expression: role of adrenoceptor-linked signaling pathways

Life Sciences
Maria KonstandiMatti A Lang

Abstract

CYP1A2, a principal catalyst for metabolism of various therapeutic drugs and carcinogens, among others, is in part regulated by the stress response. This study was designed to assess whether catecholamines and in particular adrenergic receptor-dependent pathways, modulate benzo(alpha)pyrene (B(alpha)P)-induced hepatic CYP1A2. To distinguish between the role of central and peripheral catecholamines in the regulation of CYP1A2 induction, the effect of central and peripheral catecholamine depletion using reserpine was compared to that of peripheral catecholamine depletion using guanethidine. The effects of peripheral adrenaline and L-DOPA administration were also assessed. The results suggest that alterations in central catecholamines modulate 7-methoxyresorufin O-demethylase activity (MROD), CYP1A2 mRNA and protein levels in the B(alpha)P-induced state. In particular, central catecholamine depletion, dexmedetomidine-induced inhibition of noradrenaline release and blockade of alpha(1)-adrenoceptors with prazosin, up-regulated CYP1A2 expression. Phenylephrine and dexmedetomidine-induced up-regulation may be mediated, in part, via peripheral alpha(1)- and alpha(2)-adrenoceptors, respectively. On the other hand, the L-DOPA-induced in...Continue Reading

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Citations

Jul 10, 2013·Expert Opinion on Drug Metabolism & Toxicology·Maria Konstandi
Jul 12, 2011·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Marta Kot, Władysława A Daniel
Nov 9, 2007·Life Sciences·Maria KonstandiMatti A Lang
Aug 11, 2007·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Michael KollerUNKNOWN EORTC Quality of Life Group
Nov 2, 2007·Basic & Clinical Pharmacology & Toxicology·Maria KonstandiMarios Marselos
Sep 18, 2008·Journal of Applied Toxicology : JAT·Maria KonstandiCharis Liapi
Apr 19, 2012·American Journal of Physiology. Endocrinology and Metabolism·Evangelos P DaskalopoulosMaria Konstandi
Jul 10, 2012·Molecular Pharmacology·Evangelos P DaskalopoulosMaria Konstandi
Jun 25, 2021·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Foteini MalliouMaria Konstandi

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