title: Synthesis, organotropism and hepatocellular uptake of two tritium-labeled epimers of dihydromicrocystin-LR, a cyanobacterial peptide toxin analog.
abstract: Two tritium-labeled epimers of dihydromicrocystin-LR, a derivative of the cyanobacterial peptide hepatotoxin microcystin-LR, were synthesized by reduction with sodium boro[3H]hydride and purified with reversed-phase liquid chromatography. The epimers were hepatotoxic in mice; the i.p. LD50 was 120-135 micrograms/kg. They were concentrated in the liver and to some extent in the intestine and the kidney after an i.v. injection. Freshly isolated rat hepatocytes showed a rapid uptake of both epimers. The cellular uptake of the epimers was almost complete within 5 min at concentrations 1 microM (0.5 microM dihydromicrocystin-LR + 0.5 microM microcystin-LR) and 4 microM (0.5 microM + 3.5 microM). The uptake of the earlier eluting epimer was about three times higher than that of the later eluting epimer.
authors: Abo Akademi University, Department of Biochemistry and Pharmacy, Turku, Finland.
authors: J A
authors: JA
authors: Meriluoto
authors: S E
authors: SE
authors: Nygård
authors: A M
authors: AM
authors: Dahlem
authors: J E
authors: JE
authors: Eriksson
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D000458:Cyanobacteria; D007413:Intestinal Mucosa / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008387:Marine Toxins / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000633:toxicity; D051379:Mice; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000633:toxicity
chemical_list: D008387:Marine Toxins; D010456:Peptides, Cyclic; C064961:dihydromicrocystin LR