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 cation 1-methyl-4-phenylpyridinium (MPP(+)) by primary cultured rat hepatocytes. Levamisole (500 microm) was found to produce a strong inhibition (to 31+/-2% of control) of [(3)H]MPP(+)uptake. Moreover, efflux of [(3)H]MPP(+)was also potently reduced by levamisole (500 microm). Our results show that levamisole interferes with an hepatic organic cation transporter which accepts MPP(+)as a substrate. This mechanism most probably corresponds to rOCT1, and it might be responsible for the hepatic removal of levamisole from the blood circulation. Copyright 1999 Academic Press.