title: Covalent binding of morphine to isolated rat hepatocytes.
abstract: Incubation of [3H]morphine with isolated hepatocytes caused covalent binding of [3H]-morphine to hepatocellular proteins. Sulfhydryl compounds protected against morphine-induced toxicity and decreased covalent binding. Analysis of covalently bound proteins in the cytosol by electrophoresis indicated that covalently bound radiolabel was associated with macromolecules greater than 25 kDa and increased throughout the incubation. In contrast, covalent binding to the particulate fraction was highly selectively associated with three protein bands of 50-53 and 33 kDa. Covalent binding of morphine to particulate fraction proteins was observed in hepatocytes which exhibited cellular damage. We conclude that the covalent binding of morphine to protein is associated with morphine-induced cytotoxicity.
authors.affiliation: Nihon University, College of Pharmacy, Chiba, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Nagamatsu
authors.forename: A
authors.initials: A
authors.lastname: Hasegawa
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D003600:Cytosol / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D046911:Macromolecular Substances; D008297:Male; D009020:Morphine / Q000378:metabolism* / Q000633:toxicity; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013438:Sulfhydryl Compounds / Q000494:pharmacology
chemical_list: D046911:Macromolecular Substances; D011506:Proteins; D013438:Sulfhydryl Compounds; D009020:Morphine; D005978:Glutathione