Role of adrenoceptor-linked signaling pathways in the regulation of CYP1A1 gene expression

Konstandi, Maria; Kostakis, D.; Harkitis, Panagiotis; Marselos, Marios; Johnson, Elizabeth O.; Adamidis, Konstantinos; Lang, Matti A.

doi:10.1016/j.bcp.2004.09.024

Cited by 34 publications

(35 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…An increasing body of evidence suggests that central and peripheral catecholaminergic systems play an important role in the regulation of drug-metabolizing enzymes, including the P450s (Konstandi et al, 2004(Konstandi et al, , 2005(Konstandi et al, , 2006Daskalopoulos et al, 2012). In accordance with this, the data in the present study clearly indicated a critical role for the dopaminergic pathways in P450 regulation.…”

Section: Discussionsupporting

confidence: 89%

“…Conversely, up-regulation of critical enzymes may accelerate the metabolism of drug substrate, thus leading to reduced pharmacological outcomes for the drug (Konstandi et al, 2005;Daskalopoulos et al, 2012). It is important, particularly for multidrug therapies, to be aware of the possibilities of drugdrug interactions that might lead to reduced or increased drug efficacy, severe toxicity, and/or tumorigenesis (Gonzalez and Gelboin, 1994;Guengerich, 2003;Konstandi et al, 2004;Pelkonen et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

D₂-Dopaminergic Receptor-Linked Pathways: Critical Regulators of CYP3A, CYP2C, and CYP2D

et al. 2012

Self Cite

View full text Add to dashboard Cite

Various hormonal and monoaminergic systems play determinant roles in the regulation of several cytochromes P450 (P450s) in the liver. Growth hormone (GH), prolactin, and insulin are involved in P450 regulation, and their release is under dopaminergic control. This study focused on the role of D 2 -dopaminergic systems in the regulation of the major drug-metabolizing P450s, i.e., CYP3A, CYP2C, and CYP2D. Blockade of D 2 -dopaminergic receptors with either sulpiride (SULP) or 4-(4-chlorophenyl)-1-(1H-indol-3-ylmethyl)piperidin-4-ol (L-741,626) markedly down-regulated CYP3A1/2, CYP2C11, and CYP2D1 expression in rat liver. This suppressive effect appeared to be mediated by the insulin/ phosphatidylinositol 3-kinase/Akt/FOXO1 signaling pathway. Furthermore, inactivation of the GH/STAT5b signaling pathway appeared to play a role in D 2 -dopaminergic receptor-mediated down-regulating effects on these P450s. SULP suppressed plasma GH levels, with subsequently reduced activation of STAT5b, which is the major GH pulse-activated transcription factor and has up-regulating effects on various P450s in hepatic tissue. Levels of prolactin, which exerts down-regulating control on P450s, were increased by SULP, which may contribute to SULP-mediated effects. Finally, it appears that SULP-induced inactivation of the cAMP/protein kinase A/cAMP-response element-binding protein signaling pathway, which is a critical regulator of pregnane X receptor and hepatocyte nuclear factor 1␣, and inactivation of the c-Jun N-terminal kinase contribute to SULP-induced down-regulation of the aforementioned P450s. Taken together, the present data provide evidence that drugs acting as D 2 -dopaminergic receptor antagonists might interfere with several major signaling pathways involved in the regulation of CYP3A, CYP2C, and CYP2D, which are critical enzymes in drug metabolism, thus affecting the effectiveness of the majority of prescribed drugs and the toxicity and carcinogenic potency of a plethora of toxicants and carcinogens.

show abstract

Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

D₂-Dopaminergic Receptor-Linked Pathways: Critical Regulators of CYP3A, CYP2C, and CYP2D

et al. 2012

Self Cite

View full text Add to dashboard Cite

show abstract

“…This hypothesis is strengthened by the finding that central and peripheral catecholamines appear to be involved in the regulation of CYP1A1. In this regard, peripheral catecholamines hold a potentiating role, while central noradrenergic pathways appear to be involved in down-regulation (Konstandi et al, 2004(Konstandi et al, , 2005.…”

Section: Introductionmentioning

confidence: 93%

“…Western blot analysis was performed as previously described (Konstandi et al, 2005). Briefly, microsomal proteins (10 μg) were separated by sodium dodecyl sulfate-polyacryamide gel electrophoresis for 35 min at 200 V. The proteins were then transferred by electroblotting to 0.2 μm nitrocellulose membrane.…”

Section: Western Blot Analysismentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2006

Self Cite

View full text Add to dashboard Cite

Transcription factors CncC/Maf and AhR/ARNT coordinately regulate the expression of multiple GSTs conferring resistance to chlorpyrifos and cypermethrin inSpodoptera exigua

Huang

et al. 2019

Pest Management Science

View full text Add to dashboard Cite

BACKGROUND: Glutathione S-transferases (GSTs) are a superfamily of multifunctional dimeric proteins existing in both prokaryotic and eukaryotic organisms. They are involved in the detoxification of both endogenous and exogenous electrophiles, including insecticides. However, the molecular mechanisms underlying the regulation of GST genes in insects are poorly understood. RESULTS:We first identified at least three GST genes involved in resistance to the insecticides chlorpyrifos and cypermethrin. Analysis of upstream sequences revealed that three GSTs (SeGSTo2, SeGSTe6 and SeGSTd3) harbor the same cap 'n' collar C/muscle aponeurosis fibromatosis (CncC/Maf) binding site, and SeGSTo2 and SeGSTe6 contain the aryl hydrocarbon receptor/aryl hydrocarbon receptor nuclear translocator (AhR/ARNT) binding site. Luciferase reporter assay showed co-transfection of reporter plasmid containing the SeGSTe6 promoter with CncC and/or Maf expressing constructs significantly boosted transcription. Similarly, AhR and/or ARNT expressing constructs also significantly increased the promoter activities. The co-transfection of mutated reporter plasmid with CncC/Maf or AhR/ARNT did not increase transcription activity anymore. Constitutive over-expression of CncC, Maf and AhR was also found in the HZ16 strain, which might be the molecular mechanism for up-regulated expression of multiple detoxification genes conferring resistance to insecticides. CONCLUSION: These results suggest that CncC/Maf and AhR/ARNT coordinately regulate the expression of multiple GST genes involved in insecticide resistance in Spodoptera exigua.

show abstract

Role of adrenoceptor-linked signaling pathways in the regulation of CYP1A1 gene expression

Cited by 34 publications

References 42 publications

D₂-Dopaminergic Receptor-Linked Pathways: Critical Regulators of CYP3A, CYP2C, and CYP2D

D₂-Dopaminergic Receptor-Linked Pathways: Critical Regulators of CYP3A, CYP2C, and CYP2D

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

Transcription factors CncC/Maf and AhR/ARNT coordinately regulate the expression of multiple GSTs conferring resistance to chlorpyrifos and cypermethrin inSpodoptera exigua

Contact Info

Product

Resources

About

Role of adrenoceptor-linked signaling pathways in the regulation of CYP1A1 gene expression

Cited by 34 publications

References 42 publications

D2-Dopaminergic Receptor-Linked Pathways: Critical Regulators of CYP3A, CYP2C, and CYP2D

D2-Dopaminergic Receptor-Linked Pathways: Critical Regulators of CYP3A, CYP2C, and CYP2D

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

Transcription factors CncC/Maf and AhR/ARNT coordinately regulate the expression of multiple GSTs conferring resistance to chlorpyrifos and cypermethrin inSpodoptera exigua

Contact Info

Product

Resources

About

D₂-Dopaminergic Receptor-Linked Pathways: Critical Regulators of CYP3A, CYP2C, and CYP2D

D₂-Dopaminergic Receptor-Linked Pathways: Critical Regulators of CYP3A, CYP2C, and CYP2D