title: Two significant aspects of microcystin-LR: specific binding and liver specificity.
abstract: Microcystin-LR is a unique and potent liver tumor promoter, belonging to the okadaic acid class compounds. Although microcystin-LR is a potent inhibitor of protein phosphatases 1 and 2A, as is okadaic acid, microcystin-LR has liver specificity dominance. Two significant aspects, specific binding and liver specificity of [3H]dihydromicrocystin-LR, a reduced form of microcystin-LR, were studied and compared with those of [3H]okadaic acid. [3H]-Dihydromicrocystin-LR had higher affinity for the receptors in both the particulate and cytosolic fractions of rat liver and various tissues than had [3H]okadaic acid. Intraperitoneal administration of [3H]dihydromicrocystin-LR into mice resulted in the highest uptake into the liver, 71.5 +/- 6.9% of the total administered radioactivity, whereas p.o. administration resulted in less than 1% uptake into the liver, suggesting that the mechanisms of the incorporation of microcystin-LR into the liver by i.p. and p.o. administrations are greatly different. The presence of associated forms of [3H]dihydromicrocystin-LR with macromolecules in the liver indicates a need for further investigation.
authors.affiliation: Saitama Cancer Center Research Institute, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Nishiwaki
authors.forename: T
authors.initials: T
authors.lastname: Ohta
authors.forename: E
authors.initials: E
authors.lastname: Sueoka
authors.forename: M
authors.initials: M
authors.lastname: Suganuma
authors.forename: K
authors.initials: K
authors.lastname: Harada
authors.forename: M F
authors.initials: MF
authors.lastname: Watanabe
authors.forename: H
authors.initials: H
authors.lastname: Fujiki
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000378:metabolism; D002273:Carcinogens; D003600:Cytosol / Q000378:metabolism; D005260:Female; D008099:Liver / Q000378:metabolism*; D008297:Male; D008387:Marine Toxins / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D052998:Microcystins; D010456:Peptides, Cyclic / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution
chemical_list: D001427:Bacterial Toxins; D002273:Carcinogens; D008387:Marine Toxins; D052998:Microcystins; D010456:Peptides, Cyclic; C057862:cyanoginosin LR