Abstract
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).
MeSH terms
-
ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
-
ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
-
Glyceraldehyde 3-Phosphate / genetics
-
Glyceraldehyde 3-Phosphate / metabolism
-
Humans
-
Leukocytes, Mononuclear / metabolism*
-
Liver / metabolism
-
Polymerase Chain Reaction
-
Pregnane X Receptor
-
RNA, Messenger / genetics
-
RNA, Messenger / metabolism*
-
Receptors, Cytoplasmic and Nuclear / genetics
-
Receptors, Cytoplasmic and Nuclear / metabolism*
-
Receptors, Steroid / genetics
-
Receptors, Steroid / metabolism*
Substances
-
ATP Binding Cassette Transporter, Subfamily B, Member 1
-
Pregnane X Receptor
-
RNA, Messenger
-
Receptors, Cytoplasmic and Nuclear
-
Receptors, Steroid
-
Glyceraldehyde 3-Phosphate