[Covalent binding of codeine hydroxylation products to albumin and microsomal membranes].
It was shown that incubation of rat liver microsomes with [3H] codeine in the presence of 3 mM NADPH and 0.5% albumin is accompanied by covalent binding of codeine radioactive metabolites to albumin and microsomes. At low concentrations of the microsomal protein in the samples the number of metabolites bound to the membranes is greater than those bound to albumin. At increasing concentrations of the microsomal protein the binding occurs mainly at the expense of albumin. The animal induction with phenobarbital increases the number of bound metabolites. An injection of 3-methylcholantrene does not affect the degree of binding. All typical inhibitors of cytochrome P-450, i.e. SKF-525A, methyrapone, octylamine and CO, inhibit the binding. The data obtained suggest that the metabolites which bind to the macromolecules are generated by cytochrome P-450. It is assumed that the appearance in the blood of covalently bound albumin-hapten conjugates formed in the cytochrome P-450--hydroxylase system can induce the immune response. Hense, one more protective system of the organism becomes involved in the decontamination of low molecular weight compounds.
D000418:Albumins / Q000378:metabolism*; D000818:Animals; D003061:Codeine / Q000378:metabolism*; D065607:Cytochrome P-450 Enzyme Inhibitors; D007425:Intracellular Membranes / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008862:Microsomes, Liver / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors; D011485:Protein Binding; D051381:Rats
D000418:Albumins; D065607:Cytochrome P-450 Enzyme Inhibitors; D008565:Membrane Proteins; D006899:Mixed Function Oxygenases; D003061:Codeine
Kovalentnoe sviazyvanie produktov gidroksilirovaniia kodeina s al'buminom i membranami mikrosom.