Clioquinol is sulfated by human jejunum cytosol and SULT1A3, a human-specific dopamine sulfotransferase.

Clioquinol, originally marketed as an oral intestinal amebicide, was widely used for multiple intestinal disorders. Its use as an oral agent was, however, discontinued because of its possible association with subacute myelo-optico-neuropathy or SMON. Meanwhile, its use for neurodegenerative diseases has recently been suggested. The metabolic fate of clioquinol, however, is poorly described. Since clioquinol is excreted as a sulfate in animals and humans, we have sought to identify a human sulfotransferase (SULT) responsible for the sulfation. We found that sulfating activities of human jejunal cytosols to clioquinol were well correlated with those to dopamine, a typical SULT1A3 substrate. Consistently, recombinant SULT1A3 showed the highest activity to clioquinol in vitro among the human SULTs examined. The S(50) value for the clioquinol sulfation by SULT1A3 was similar to the K(m) value for that by cytosols from human jejunum, where SULT1A3 is abundantly expressed. Moreover, clioquinol inhibited both human jejunal cytosol- and SULT1A3-mediated sulfations of dopamine in a dose-dependent manner, showing similar IC(50) values. These results suggest that SULT1A3, which is highly expressed in intestine but not in liver, is responsible for the clioquinol sulfation in humans, raising a possibility that orally administered clioquinol might inhibit dopamine sulfation in human intestines.