The pig as a model for studying AH receptor and other PAH-binding proteins in man.
In this report we compare the three major binding proteins existing in hepatic cytosols of pig and human. Many data suggest that for the AH receptor, which mediates the biological effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin, a structural as well as a functional variability exists across species. Similar conclusions can be drawn from the interspecies characterization of benzo(a)pyrene binding proteins, namely the 4S protein and the 8S protein. Using fractionation procedures such as sucrose gradient sedimentation and gel permeation chromatography we obtained enriched fractions containing each of these binding proteins. By saturation experiments and analysis of data by Scatchard and Woolf plots we determined binding characteristics and we conclude that pig and human AH receptors were closely related proteins since their Kd (18 +/- 0.4nM) were found quite similar. On the other hand, 4S proteins from pig (Kd = 16.7 nM; Bmax = 5.5 pmol/mg) and from human (Kd = 14 nM; Bmax = 4.5 pmol/mg) as well as 8S proteins (Kd approximately 300 nM) also exhibit remarkable similarities.
Lesca
P
P
Laboratoire de Pharmacologie et Toxicologie, INRA, Toulouse, France.
Witkamp
R
R
Maurel
P
P
Galtier
P
P
D000818:Animals; D001667:Binding, Competitive; D002352:Carrier Proteins / Q000302:isolation & purification / Q000378:metabolism*; D002499:Centrifugation, Density Gradient; D002850:Chromatography, Gel; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D000072317:Polychlorinated Dibenzodioxins / Q000378:metabolism*; D011083:Polycyclic Compounds / Q000378:metabolism*; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects / Q000378:metabolism*; D013552:Swine
D002352:Carrier Proteins; D000072317:Polychlorinated Dibenzodioxins; D011083:Polycyclic Compounds; D018336:Receptors, Aryl Hydrocarbon