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X Demographics
Mendeley readers
Attention Score in Context
| Title |
D2-Dopaminergic Receptor-Linked Pathways: Critical Regulators of CYP3A, CYP2C, and CYP2D
|
|---|---|
| Published in |
Molecular Pharmacology, July 2012
|
| DOI | 10.1124/mol.112.078709 |
| Pubmed ID | |
| Authors |
Evangelos P. Daskalopoulos, Matti A. Lang, Marios Marselos, Foteini Malliou, Maria Konstandi |
| Abstract |
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 D₂-dopaminergic systems in the regulation of the major drug-metabolizing P450s, i.e., CYP3A, CYP2C, and CYP2D. Blockade of D₂-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 D₂-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 1α, 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 D₂-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. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 24 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 24 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 7 | 29% |
| Researcher | 7 | 29% |
| Student > Doctoral Student | 3 | 13% |
| Student > Bachelor | 2 | 8% |
| Professor | 1 | 4% |
| Other | 1 | 4% |
| Unknown | 3 | 13% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 7 | 29% |
| Biochemistry, Genetics and Molecular Biology | 4 | 17% |
| Neuroscience | 2 | 8% |
| Psychology | 2 | 8% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 4% |
| Other | 3 | 13% |
| Unknown | 5 | 21% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 23 December 2012.
All research outputs
#20,724,339
of 23,323,574 outputs
Outputs from Molecular Pharmacology
#3,192
of 3,308 outputs
Outputs of similar age
#149,290
of 165,488 outputs
Outputs of similar age from Molecular Pharmacology
#23
of 23 outputs
Altmetric has tracked 23,323,574 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 3,308 research outputs from this source. They receive a mean Attention Score of 4.8. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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We're also able to compare this research output to 23 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.