Dexamethasone The nuclear receptor PXR is a direct regulator of CYP3A in rat Sample Clauses

Dexamethasone The nuclear receptor PXR is a direct regulator of CYP3A in rat. It is also has the ability to cross-talk with CAR by binding to the PB-response elements that regulate CYP2B (Wei, Zhang, Dowhan, Han, & Xxxxx, 2002). To further delineate whether or not the decrease in CYP3A2 expression with PB and some AHR agonists was mediated through a PXR: AHR interaction two efficacious rat PXR ligands, dexamethasone (DEX) and pregnenolone-16α-carbonitrile (PCN), were used (XxXxxxxx, 2001). Dexamethasone, a synthetic glucorticoid, has been used previously as an activator of rat PXR as well as human PXR and induces CYP3A gene expression (Xxxxxxx, et al., 2004) (Pascussi, Drocourt, Fabre, Maurel, & Vilarem, 2000). Some studies have shown that dexamethasone is capable of inducing murine CYP2B but this induction is dependent on the glucorticoid receptor (Xxxxx-Xxxxx & Xxxxxxxx, 2009); however, the induction of CYP3A is most sensitive to glucorticoids like dexamethasone (Monostory & Vereczkey, 1994) and reports of dexamethasone inducing rat CYP2B via PXR were not found. Combinational studies with 20 µM DEX in combination with different concentrations of β-NF (1 µM-100 µM) were performed. After 48 hours of exposure to DEX with or without x-XX, XXX0X0 protein levels were observed. At all concentrations of β-NF with 20 µM DEX there was an increase in CYP3A2 when compared to DEX alone. Furthermore, concomitant treatment with β-NF and DEX did not decrease CYP3A2 protein expression at all (Figure 3.5a).