Kanno K, Sasaki S, Hirata Y, Ishikawa S, Fushimi K, Nakanishi S, Bichet D G, Marumo F
Second Department of Internal Medicine, School of Medicine, Tokyo Medical and Dental University, Japan.
N Engl J Med. 1995 Jun 8;332(23):1540-5. doi: 10.1056/NEJM199506083322303.
Urine-concentrating ability is regulated by vasopressin. Recently, the specific water-channel protein of the renal collecting duct, known as aquaporin-2, was cloned. However, it is not certain whether this molecule is responsive to vasopressin.
We measured the urinary excretion of aquaporin-2 and its response to vasopressin in 11 normal subjects and 9 patients with central or nephrogenic diabetes insipidus. The urine samples were collected during periods of dehydration and hydration and after the administration of vasopressin. Urine samples were analyzed for aquaporin-2 by the Western blot assay and immunogold labeling, and the amount of aquaporin-2 was determined by radioimmunoassay.
Aquaporin-2 was detectable in the urine in both soluble and membrane-bound forms. In the five normal subjects tested, the mean (+/- SE) urinary excretion of aquaporin-2 was 11.2 +/- 2.2 pmol 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 urinary excretion of aquaporin-2 from 0.8 +/- 0.3 to 11.2 +/- 1.6 pmol per milligram of creatinine (P < 0.001). The five patients with central diabetes insipidus also had increases in urinary excretion of aquaporin-2 in response to the administration of vasopressin, but the four patients with X-linked or non-X-linked nephrogenic diabetes insipidus did not.
Aquaporin-2 is detectable in the urine, and changes in the urinary excretion of this protein can be used as an index of the action of vasopressin on the kidney.
尿液浓缩能力受抗利尿激素调节。最近，肾集合管的特异性水通道蛋白——水通道蛋白-2被克隆出来。然而，尚不确定该分子是否对抗利尿激素有反应。
我们测定了11名正常受试者和9名中枢性或肾性尿崩症患者尿液中水通道蛋白-2的排泄情况及其对抗利尿激素的反应。在脱水期、水化期以及给予抗利尿激素后收集尿液样本。通过蛋白质免疫印迹分析和免疫金标记法对尿液样本进行水通道蛋白-2分析，并通过放射免疫分析法测定水通道蛋白-2的含量。
尿液中可检测到可溶性和膜结合形式的水通道蛋白-2。在接受检测的5名正常受试者中，脱水一段时间后，水通道蛋白-2的平均（±标准误）尿排泄量为每毫克肌酐11.2±2.2皮摩尔，在水化期后的第二个小时降至每毫克肌酐3.9±1.9皮摩尔（P = 0.03）。在其他6名正常受试者中，静脉输注去氨加压素（1-去氨基-8-D-精氨酸加压素）使水通道蛋白-2的尿排泄量从每毫克肌酐0.8±0.3皮摩尔增加至11.2±1.6皮摩尔（P < 0.001）。5名中枢性尿崩症患者在给予抗利尿激素后水通道蛋白-2的尿排泄量也增加，但4名X连锁或非X连锁肾性尿崩症患者则没有。
尿液中可检测到水通道蛋白-2，该蛋白尿排泄量的变化可作为抗利尿激素对肾脏作用的一个指标。
