Identification of a novel target of thiazide diuretics

Thiazide diuretics are the older but still one of the most effective therapies for human hypertension. They are believed to act exclusively by blocking renal sodium absorption by the NaCl cotransporter NCC. We recently identified, however, a novel NaCl transport system that is expressed in intercalated cells of the collecting duct. This novel mechanism of NaCl transport operates by the combined action of 2 chloride/bicarbonate exchangers, 1 sodium-independent and 1 sodium-dependent. We propose that part of the action of thiazide occurs through blockade of this novel system.