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• W2102426774 endingPage "E54" @default.
• W2102426774 startingPage "E40" @default.
• W2102426774 abstract "Stress is a critical player in the regulation of the major cytochrome P-450s ( CYPs) that metabolize the majority of the prescribed drugs. Early in life, maternal deprivation (MD) stress and repeated restraint stress (RS) modified CYP expression in a stress-specific manner. In particular, the expression of CYP3A1 and CYP2C11 was increased in the liver of MD rats, whereas RS had no significant effect. In contrast, hepatic CYP2D1/2 activity was increased by RS, whereas MD did not affect it. The primary effectors of the stress system, glucocorticoids and epinephrine, highly induced CYP3A1/2. Epinephrine also induced the expression of CYP2C11 and CYP2D1/2. Further investigation indicated that AR-agonists may modify CYP regulation. In vitro experiments using primary hepatocyte cultures treated with the AR-agonists phenylephrine, dexmedetomidine, and isoprenaline indicated an AR-induced upregulating effect on the above-mentioned CYPs mediated by the cAMP/protein kinase A and c-Jun NH 2 -terminal kinase signaling pathways. Interestingly though, in vivo pharmacological manipulations of ARs using the same AR-agonists led to a suppressed hepatic CYP expression profile, indicating that the effect of the complex network of central and peripheral AR-linked pathways overrides that of the hepatic ARs. The AR-mediated alterations in CYP3A1/2, CYP2C11, and CYP2D1/2 expressions are potentially connected with those observed in the activation of signal transducer and activator of transcription 5b. In conclusion, stress and AR-agonists may modify the expression of the major CYP genes involved in the metabolism of drugs used in a wide range of diseases, thus affecting drug efficacy and toxicity." @default.
• W2102426774 created "2016-06-24" @default.
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• W2102426774 date "2012-07-01" @default.
• W2102426774 modified "2023-10-18" @default.
• W2102426774 title "Stress is a critical player in<i>CYP3A</i>,<i>CYP2C</i>, and<i>CYP2D</i>regulation: role of adrenergic receptor signaling pathways" @default.
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• W2102426774 doi "https://doi.org/10.1152/ajpendo.00545.2011" @default.
• W2102426774 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22510709" @default.
• W2102426774 hasPublicationYear "2012" @default.
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