Expression of pregnane-X-receptor transcript in peripheral blood mononuclear cells and correlation with MDR1 mRNA.
P-glycoprotein (P-gp) limits bioavailability and accumulation of HIV protease inhibitors (PIs). PIs are ligands for the pregnane-X-receptor (PXR), which regulates P-gp expression. This occurs when ligands activate the receptor, initiating binding to response elements in the MDR1 promoter. PXR also activates cytochrome P4503A4 (CYP3A4) and a correlation between hepatic PXR and CYP3A4 mRNA has been reported. We have examined the relationship between MDR1 and PXR mRNA in peripheral blood cells and demonstrate a significant correlation in 18 volunteers (R2=0.4; P<0.005). PXR was approximately 250-fold lower in peripheral blood mononuclear cells than in liver (1.6+/-1.2 vs 450+/-298; n=6; P<0.01).
Owen
Andrew
A
Department of Pharmacology and Therapeutics, The University of Liverpool, Liverpool, UK. aowen@liv.ac.uk
Chandler
Becky
B
Back
Dave J
DJ
Khoo
Saye H
SH
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D005986:Glyceraldehyde 3-Phosphate / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D016133:Polymerase Chain Reaction; D000077297:Pregnane X Receptor; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D011987:Receptors, Steroid / Q000235:genetics / Q000378:metabolism*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000077297:Pregnane X Receptor; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D005986:Glyceraldehyde 3-Phosphate