Vasopressin-dependent upregulation of aquaporin-2 gene expression in glucocorticoid-deficient rats.
We determined alterations in renal aquaporin-2 (AQP2) gene expression in association with impaired water excretion in glucocorticoid-deficient rats. After adrenalectomy, Sprague-Dawley rats were administered aldosterone alone by osmotic pumps (glucocorticoid-deficient rats). As a control, both aldosterone and dexamethasone were administered. These animals were subjected to the studies on days 7-14. The expressions of AQP2 mRNA and protein in kidney of the glucocorticoid-deficient rats were increased by 1.6- and 1.4-fold compared with the control rats, respectively. An acute oral water load test verified the marked impairment in water excretion in the glucocorticoid-deficient rats. One hour after the water load, the expressions of AQP2 mRNA and protein were significantly reduced in the control rats, but they remained unchanged in the glucocorticoid-deficient rats. However, there was no alteration in [(3)H]arginine vasopressin (AVP) receptor binding and AVP V(2) receptor mRNA expression in the glucocorticoid-deficient rats. A V(2)-receptor antagonist abolished the increased expressions of AQP2 mRNA and protein in the glucocorticoid-deficient rats. These results indicate that augmented expression of AQP2 participates in impaired water excretion, dependent on AVP, in glucocorticoid deficiency.
Saito
T
T
Division of Endocrinology and Metabolism, Department of Medicine, Jichi Medical School, Tochigi 329-0498, Japan.
Ishikawa
S E
SE
Ando
F
F
Higashiyama
M
M
Nagasaka
S
S
Sasaki
S
S
D000315:Adrenalectomy; D000450:Aldosterone / Q000494:pharmacology; D000818:Animals; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins / Q000235:genetics* / Q000378:metabolism; D001127:Arginine Vasopressin / Q000378:metabolism*; D015152:Blotting, Northern; D004326:Drinking / Q000502:physiology*; D015870:Gene Expression / Q000502:physiology; D005938:Glucocorticoids / Q000172:deficiency*; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017483:Receptors, Vasopressin / Q000378:metabolism; D012964:Sodium / Q000097:blood; D014316:Tritium; D014867:Water / Q000378:metabolism
C496025:Aqp2 protein, rat; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins; D005938:Glucocorticoids; D012333:RNA, Messenger; D017483:Receptors, Vasopressin; D014867:Water; D014316:Tritium; D001127:Arginine Vasopressin; D000450:Aldosterone; D012964:Sodium