THE UPTAKE OF THE CYANOBACTERIAL HEPATOTOXIN MICROCYSTIN BY ISOLATED RAT HEPATOCYTES

Microcystin-YM a cyclic heptapeptide hepatotoxin isolated from the cyanobacterium Microcystis aeruginosa was radiolabeled with I-125, and used to investigate the uptake of the toxin by freshly isolated rat hepatocytes. The uptake was temperature dependent with apparent activation energy of 18 kcal/mole (77kJ/mole) for the initial rate of uptake. Uptake of non-toxic (10-20nM) doses of microcystin by hepatocytes continued with time, the intracellular to extracellular distribution ratio for the toxin was 70 at 60 min for 10(6) cells/ml. Uptake of higher doses of microcystin (100 nM and more) stopped when the cells blebbed: a toxic response of hepatocytes to microcystin. Uptake of microcystin by hepatocytes was inhibited 70-80% by the addition of 10 mu-M sodium deoxycholate or bromsulphthlein, compounds that protect hepatocytes from the toxic effects of microcystin.