Background Urine-concentrating ability is regulated by vasopressin.Recently, the specific water-channel protein of the renal collectingduct, known as aquaporin-2, was cloned. However, it is not certainwhether this molecule is responsive to vasopressin.
Methods We measured the urinary excretion of aquaporin-2 andits response to vasopressin in 11 normal subjects and 9 patientswith central or nephrogenic diabetes insipidus. The urine sampleswere collected during periods of dehydration and hydration andafter the administration of vasopressin. Urine samples wereanalyzed for aquaporin-2 by the Western blot assay and immunogoldlabeling, and the amount of aquaporin-2 was determined by radioimmunoassay.
Results Aquaporin-2 was detectable in the urine in both solubleand membrane-bound forms. In the five normal subjects tested,the mean (±SE) urinary excretion of aquaporin-2 was 11.2±2.2pmol per milligram of creatinine after a period of dehydration,and it decreased to 3.9±1.9 pmol per milligram of creatinine(P = 0.03) during the second hour after a period of hydration.In the six other normal subjects, an infusion of desmopressin(1-desamino-8-d-arginine vasopressin) increased the urinaryexcretion of aquaporin-2 from 0.8±0.3 to 11.2±1.6pmol per milligram of creatinine (P<0.001). The five patientswith central diabetes insipidus also had increases in urinaryexcretion of aquaporin-2 in response to the administration ofvasopressin, but the four patients with X-linked or non–X-linkednephrogenic diabetes insipidus did not.
Conclusions Aquaporin-2 is detectable in the urine, and changesin the urinary excretion of this protein can be used as an indexof the action of vasopressin on the kidney.
Source Information
From the Second Department of Internal Medicine, School of Medicine, Tokyo Medical and Dental University, Tokyo (K.K., S.S., Y.H., K.F., F.M.); the Department of Endocrinology and Metabolism, Jichi Medical School, Tochigi (S.I.); and Pharmaceutical Basic Research Laboratories, Central Pharmaceutical Research Institute, JT Inc., Kanagawa (S.N.) — all in Japan; and the Centre de Recherche, Hôpital du Sacré-Coeur, University of Montreal, Montreal (D.G.B).
Address reprint requests to Dr. Sasaki at the Second Department of Internal Medicine, School of Medicine, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-Ku, Tokyo 113, Japan.
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