Detection of a nafenopin-binding protein in rat liver cytosol associated with the induction of peroxisome proliferation by hypolipidemic compounds.
[3H]nafenopin, a known inducer of liver peroxisomal enzymes, was shown to bind to a specific, saturable pool of binding sites in cytosols from rat liver and kidney cortex. Tissue levels of this binding protein (liver greater than kidney cortex; not detectable in myocardium, skeletal muscle) were seen to correlate with the ability of nafenopin to induce peroxisomal enzymes in these organs. Clofibrate and ciprofibrate, which are structurally similar to nafenopin, competitively blocked the specific binding of [3H]nafenopin. Phenobarbital, a non-inducer of peroxisomes, and [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio]acetic acid and 4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio(N-beta-hydroxyethyl)acetamide, which are structurally unrelated peroxisome proliferators, did not complete for the specific [3H]nafenopin binding sites. The [3H]nafenopin binding protein is proposed as a mediator of the drug-induced increase in peroxisomes and associated peroxisomal enzymes.
D000818:Animals; D002352:Carrier Proteins / Q000032:analysis*; D002994:Clofibrate / Q000494:pharmacology; D002995:Clofibric Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D003600:Cytosol / Q000032:analysis; D004790:Enzyme Induction; D058607:Fibric Acids; D007672:Kidney Cortex / Q000032:analysis; D008099:Liver / Q000032:analysis / Q000378:metabolism*; D008297:Male; D008830:Microbodies / Q000201:enzymology*; D009255:Nafenopin / Q000378:metabolism*; D011422:Propionates / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344
D002352:Carrier Proteins; D058607:Fibric Acids; D011422:Propionates; D009255:Nafenopin; D002995:Clofibric Acid; C019304:ciprofibrate; D002994:Clofibrate