Differential effects of microsomal enzyme–inducing chemicals on the hepatic expression of rat organic anion transporters, OATP1 and OATP2

@article{RauschDerra2001DifferentialEO,
  title={Differential effects of microsomal enzyme–inducing chemicals on the hepatic expression of rat organic anion transporters, OATP1 and OATP2},
  author={Lesley C. Rausch-Derra and Dylan P. Hartley and Peter J. Meier and Curtis D. Klaassen},
  journal={Hepatology},
  year={2001},
  volume={33}
}
The organic anion transporting polypeptides, Oatp1 (Slc21a1) and Oatp2 (Slc21a5), mediate hepatic uptake of cardiac glycosides. Previously, we demonstrated that chemicals that increase cytochrome P450s differentially affect hepatic uptake of cardiac glycosides. We postulated that increased uptake of cardiac glycosides observed after pretreatment of animals with phenobarbital (PB) and pregnenolone‐16α‐carbonitrile (PCN) occurs via increased hepatic expression of Oatp1 and/or Oatp2. Male Sprague… 

Induction profile of rat organic anion transporting polypeptide 2 (oatp2) by prototypical drug-metabolizing enzyme inducers that activate gene expression through ligand-activated transcription factor pathways.

To determine whether oatp2 is regulated by a broader scale of drug-metabolizing enzyme inducers that are ligands or activators for the aryl hydrocarbon receptor (AhR), constitutive androstane receptor (CAR), pregnane X receptor (PXR), peroxisome proliferator-activated receptor (PPAR), and antioxidant/electrophile response element (ARE/EpRE), the purpose of this study was to further determine.

REGULATION OF MOUSE ORGANIC ANION-TRANSPORTING POLYPEPTIDES (OATPS) IN LIVER BY PROTOTYPICAL MICROSOMAL ENZYME INDUCERS THAT ACTIVATE DISTINCT TRANSCRIPTION FACTOR PATHWAYS

It is hypothesized that expression of Oatps and biotransformation enzymes is coordinately regulated in liver, and only a few transcription factor activators increased Oatp expression, and, surprisingly, many decreased OatP expression.

Tissue expression, ontogeny, and inducibility of rat organic anion transporting polypeptide 4.

The preference of Oatp4 for endogenous compounds coupled with its refractory response to known drug-metabolizing enzyme inducers suggests that Oat p4 may be largely responsible for the homeostasis of endogenous rather than exogenous chemicals, including pharmaceuticals.

Induction of rat organic anion transporting polypeptide 2 by pregnenolone-16alpha-carbonitrile is via interaction with pregnane X receptor.

The rat organic anion transporting polypeptide 2 (oatp2; Slc21a5) is a liver transporter that mediates the uptake of a variety of structurally diverse compounds, and has a high affinity for cardiac

Postnatal expression and induction by pregnenolone-16alpha-carbonitrile of the organic anion-transporting polypeptide 2 in rat liver.

Rat oatp2 undergoes age-dependent and chemical regulation during postnatal development, and is a potential target for drug-drug and age-drug interactions.

Role of rat multidrug resistance protein 2 in plasma and biliary disposition of dibromosulfophthalein after microsomal enzyme induction.

The increase in Mrp2 protein after microsomal enzyme induction is responsible for increased biliary DBSP excretion and the importance of compensatory hepatic transporters in eliminating DBSP by alternative pathways other thanMrp2 is demonstrated.

Induction of hepatic phase II drug-metabolizing enzymes by 1,7-phenanthroline in rats is accompanied by induction of MRP3.

Data indicated that PH induced mRNA levels of the efflux transporter, Mrp3, which may also affect the disposition of xenobiotic transporters and drug-metabolizing enzymes.

Transport of the sulfated, amidated bile acid, sulfolithocholyltaurine, into rat hepatocytes is mediated by Oatp1 and Oatp2

The results suggest that transport of SLCT into rat liver is mediated in part by Oatp1 and OatP2, high-affinity pathways, a lower‐affinity pathway of unknown origin, and a nonsaturable pathway that is compatible with a transport system of high Km and/or passive diffusion.

Effect of microsomal enzyme inducers on the biliary excretion of triiodothyronine (T(3)) and its metabolites.

  • N. VansellC. Klaassen
  • Biology, Medicine
    Toxicological sciences : an official journal of the Society of Toxicology
  • 2002
Findings indicate that PCN increases the glucuronidation and biliary excretion of T(3) in vivo, and suggest that enhanced elimination of T (3) may be the mechanism responsible for the increases in serum TSH caused by PCN.

Mechanisms by Which Inducers of Drug Metabolizing Enzymes Alter Thyroid Hormones in Rats

Information about inducible thyroid hormone transport into and out of liver, beyond induction of glucuronidation, should be considered and applied to screening and risk assessment paradigms when assessing an inducer’s potential to alter thyroid homeostasis in nonclinical species and humans.
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