Disclosed is a method for detecting an aquaretic compound. In one embodiment, the method includes administering to a mammal a candidate compound that modulates a nociceptin receptor. Biological material is isolated from the mammal and expression of aquaporin-2 is measured. Modulation of the aquaporin-2 is taken to be indicative of a candidate compound having aquaretic activity. The invention has a wide spectrum of uses including helping to identify new diuretics that spare unwanted loss of sodium and potassium ions.