Inhibition by levamisole of the organic cation transporter rOCT1 in cultured rat hepatocytes

Levamisole is known to be subject to hepatic removal and metabolism and to biliary excretion. The aim of our work was to study the mechanism involved in the removal of this compound by the liver. For this purpose, we studied the influence of levamisole on the uptake and efflux of the model organic c ation 1-methyl-4-phenylpyridinium (MPP+) by primary cultured rat hepatocyte s. Levamisole (500 mu M) was found to produce a strong inhibition (to 31 +/ - 2% of control) of [H-3]MPP+ uptake. Moreover, efflux of [3H]MPP+ was also potently reduced by levamisole (500 mu M). Our results show that levamisol e interferes with an hepatic organic cation transporter which accepts MPPas a substrate. This mechanism most probably corresponds to rOCT1, and it m ight be responsible for the hepatic removal of levamisole from the blood ci rculation.