2 metabolism Aryl hydrocarbon receptor

H. (2005) Role of the aryl hydrocarbon receptor in drug metabolism. Expert Opinion on Drug Metabolism ej Toxicology,... 

Many of the planar PAH compounds induce their own metabolism by inducing transcription of the aryl hydrocarbon receptor (Ah receptor). Although expression of CYP1A1 and 1A2 is often coordinately induced, there are clear differences in regulation, not only with respect to substrate specificity but also in their biological expression. For example, CYP1A1 does not appear to be expressed in human liver unless induced,... 

Bhattacharyya KK, Brake PB, Eltom SE, Otto SA, Jeffcoate CR. Identification of a rat adrenal cytochrome P450 active in polycyclic-hydrocarbon metabolism as rat CYPIBI demonstration of a unique tissue-specific pattern on hormonal and aryl-hydrocarbon receptor-linked regulation. J. Biol. Chem. 1995 270 11595-11602. 

Andreola F, Fernandez-Salguero PM, Chiantore MV, Petkovich MP, Gonzalez FJ, De Luca LM. 1997. Aryl hydrocarbon receptor knockout mice (AHR—/—) exhibit liver retinoid accumulation and reduced retinoic acid metabolism. Cancer Res. 57 2835-38... 

White, R.D., D. Shea and J.J. Stegeman. Metabolism of the aryl hydrocarbon receptor agonist 3,3, 4, 4 tetrachlorobiphenyl by the marine fish scup (Stenotomus chrysops) in vivo and in vitro. Drug Metab. Dispos. 25 564-572, 1997. 

Bello, S.M., D.G. Franks, J.J. Stegeman and M.E. Hahn. Acquired resistance to aryl hydrocarbon receptor agonists in a population of Fundulus heteroclitus from a marine Superfund site in vivo and in vitro studies on the induction of xenobiotic-metabolizing enzymes. Toxicol. Sci. 60 77—91, 2001. 

Miao, W., Hu, L., Scrivens, P. J., and Batist, G. (2005) Transcriptional regulation of NF-E2 p45-related factor (NRF2) expression by the aryl hydrocarbon receptor-xenobiotic response element signaling pathway direct cross-talk between phase I and II drug-metabolizing enzymes../. Biol. Chem. 280, 20340-20348. 

In this chapter, we will review the creation of various mouse models of xenobiotic nuclear receptors, and the utilization of mouse models in drug metabolism studies and drug development. Special emphasis will put on the mouse models humanized for the nuclear receptors or the aryl hydrocarbon receptor (AhR), which is a nonnuclear receptor xenobiotic receptor. 

Fig. 8 Ligands of the aryl hydrocarbon receptor (AHR), exemplified by the environmental chemical benzo[a]pyrene (B[a]P), induce their own metabolism by cytochromes P450 (CYPs), resulting in their enhanced elimination or bioactivation to potentially toxic reactive intermediates...

Hassoun EA, Walter AC, Alsharif NZ, Stohs SJ (1997) Modulation of TCDD-induced fetotoxicity and oxidative stress in embryonic and placental tissues of C57BL/6J mice by vitamin E succinate and ellagic acid. Toxicology 124 27-37 Hemandez-Ochoa I, Karman BN, Flaws JA (2009) The role of the aryl hydrocarbon receptor in the female reproductive system. Biochem Pharmacol 77 547-559 Hines RN (2008) The ontogeny of drug metabolism enzymes and implications for adverse drug events. Pharmacol Ther 118 250-267... 

Nishimura N, Yonemoto J, Miyabara Y, Fujii-Kuriyama Y, Tohyama C (2005) Altered thyroxin and retinoid metabolic response to 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin in aryl hydrocarbon receptor-null mice. Arch Toxicol 79 260-267... 

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