Ligand-dependent assembly of pregnane X receptor, constitutive androstane receptor and liver X receptor is applicable to identify ligands.
Pregnane X receptor (PXR), constitutive androstane receptor (CAR) and liver X receptor (LXR) are intracellular sensors for foreign chemicals and/or endogenous compounds. Docking of a ligand into the ligand-binding domain (LBD) of a nuclear receptor induces conformational changes and switches the nuclear receptor into an active conformation. In this study, we examined whether assembly assays to exploit the ligand-dependent interaction of N- and C-terminal regions of the LBD could be used for detection of ligands for PXR, CAR and LXR. Rifampicin, CITCO and T1317 significantly enhanced interactions for human PXR, human CAR and human LXR, respectively. The effects of ligands on the interaction of LBDs in PXR and CAR reflected the species differences in ligand response of PXR and CAR. In conclusion, it appears that the present assay, which exploits the interaction between N- and C-terminal regions of LBDs, is applicable to identify ligands.
Kobayashi
Kaoru
K
Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan. kaoruk@p.chiba-u.ac.jp.
Saito
Kosuke
K
Takagi
Sachiko
S
Chiba
Kan
K
D000818:Animals; D001665:Binding Sites; D000090702:Constitutive Androstane Receptor; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008024:Ligands; D000071518:Liver X Receptors; D051379:Mice; D057093:Orphan Nuclear Receptors / Q000096:biosynthesis*; D010957:Plasmids; D000077297:Pregnane X Receptor; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis*; D011987:Receptors, Steroid / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection
D000090702:Constitutive Androstane Receptor; D008024:Ligands; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D000077297:Pregnane X Receptor; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D011994:Recombinant Proteins