The tubular secretion of diuretics in the proximal tubule has been shown to be critical for the action of drugs. To elucidate the molecular mechanisms for the tubular excretion of diuretics, we have elucidated the interactions of human organic anion transporters (hOATs) with diuretics using cells stably expressing hOATs. Diuretics tested were thiazides, including chlorothiazide, cyclothiazide, hydrochlorothiazide, and trichlormethiazide; loop diuretics, including bumetanide, ethacrynic acid, and furosemide; and carbonic anhydrase inhibitors, including acetazolamide and methazolamide. These diuretics inhibited organic anion uptake mediated by hOAT1, hOAT2, hOAT3, and hOAT4 in a competitive manner. hOAT1 exhibited the highest affinity interactions for thiazides, whereas hOAT3 did those for loop diuretics. hOAT1, hOAT3, and hOAT4 but not hOAT2, mediated the uptake of bumetanide. hOAT3 and hOAT4, but not hOAT1 mediated the efflux of bumetanide. hOAT1 and hOAT3, but not hOAT2 and hOAT4 mediated the uptake of furosemide. In conclusion, it was suggested that hOAT1 may play an important role in the basolateral uptake of thiazides, and hOAT3 in the uptake of loop diuretics. In addition, it was also suggested that bumetanide taken up by hOAT3 and/or hOAT1 is excreted into the urine by hOAT4.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.