PT  - JOURNAL ARTICLE
AU  - Hasannejad, Habib
AU  - Takeda, Michio
AU  - Taki, Kentarou
AU  - Shin, Ho Jung
AU  - Babu, Ellappan
AU  - Jutabha, Promsuk
AU  - Khamdang, Suparat
AU  - Aleboyeh, Mahmoud
AU  - Onozato, Maristela Lika
AU  - Tojo, Akihiro
AU  - Enomoto, Atsushi
AU  - Anzai, Naohiko
AU  - Narikawa, Shinichi
AU  - Huang, Xiu-Lin
AU  - Niwa, Toshimitsu
AU  - Endou, Hitoshi
TI  - Interactions of Human Organic Anion Transporters with Diuretics
AID  - 10.1124/jpet.103.059139
DP  - 2004 Mar 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1021--1029
VI  - 308
IP  - 3
4099  - http://jpet.aspetjournals.org/content/308/3/1021.short
4100  - http://jpet.aspetjournals.org/content/308/3/1021.full
SO  - J Pharmacol Exp Ther2004 Mar 01; 308
AB  - 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. The American Society for Pharmacology and Experimental Therapeutics