Two significant aspects of microcystin-LR: specific binding and liver specificity.

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.