1 Division of Endocrinology and Metabolism, Department of Medicine, Jichi Medical School, Tochigi 329-0498; and 2 Second Department of Internal Medicine, Tokyo Medical and Dental University, Tokyo 113-0034, Japan
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ABSTRACT |
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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 [3H]arginine vasopressin (AVP) receptor binding and AVP V2 receptor mRNA expression in the glucocorticoid-deficient rats. A V2-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.
arginine vasopressin; water retention
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INTRODUCTION |
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CLINICAL AND LABORATORY EXPERIMENTS have demonstrated that impairment in water excretion occurs in patients with hypopituitarism and adrenal insufficiency (1, 11, 15, 32) and in experimental models of glucocorticoid and mineralocorticoid deficiency (7, 13, 17, 22, 25, 31). The phenomenon has been investigated extensively, and there is evidence that arginine vasopressin (AVP) plays a role in impaired water excretion in such pathological states (1, 11, 13, 17). We showed the removal of water retention by the AVP V2-receptor antagonist in rats with glucocorticoid deficiency (13).
AVP produces the water permeability of renal collecting duct, and its action is mediated by cAMP (10, 16). Aquaporin-2 (AQP2) is a water channel in the apical collecting duct in the kidney (6, 30). The cAMP-responsive element is found in the 224 bp of the 5'-flanking region of the AQP2 gene, which contains the element necessary for the cAMP-induced regulatory mechanism (18, 34). AVP is known to be the important regulator of the transcription rates of the AQP2 gene (9, 18). When the cells are stimulated by AVP, AQP2 is translocated from cytoplasmic vesicles to apical plasma membranes, by shuttle trafficking, in collecting duct cells (19, 26, 36). AQP2 is again redistributed into cytoplasmic vesicles after removal of AVP stimulation (28). Recent studies have shown the upregulation of AQP2 mRNA expression in kidney in the pathological state of water retention in experimental models of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), liver cirrhosis with ascites, and congestive heart failure (2, 5, 20, 35).
The present study was undertaken to determine whether AQP2 is involved in pathogenesis of impaired water excretion in rats with experimental model of glucocorticoid deficiency. Also, we examined what alteration in AVP V2 receptors is found in glucocorticoid deficiency.
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METHODS |
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Animals.
Male Sprague-Dawley (SD) rats weighing 250-300 g were used in the
present experiments. The animals were housed individually in metabolic
cages at a temperature of 21-23°C with the lights on from 8 AM
to 8 PM. Solid food and water were available ad libitum during the
experimental period. Under light ether anesthesia, the animals were
adrenalectomized through bilateral retroperitoneal incisions, and then
osmotic pumps (Alza model 2ML4, Palo Alto, CA) were implanted
subcutaneously along their backs. The adrenalectomized rats were
divided into two groups. A group of glucocorticoid-deficient rats was
administered aldosterone at a rate of 42 ng · 100 g1 · h
1 by osmotic pumps throughout
the experiments (4). The other group of rats (control) was
administered both aldosterone (42 ng · 100 g
1
· h
1) and dexamethasone (58 ng · 100 g
1 · h
1) by osmotic pumps throughout
the experiments. After the recovery, they were placed in cages with
free access to water and rat chow. The two groups of rats were
subjected to the following studies on days 7-14.
One-milliliter blood collections were made to determine serum sodium
and plasma osmolality (Posm). After the completion of
sampling, the animals were killed by decapitation. Blood from the trunk
was collected to measure plasma AVP levels. Both kidneys were removed
to determine AQP2 mRNA and AQP2 protein expression, AVP V2
receptor mRNA expression, and AVP receptor binding. Posm was measured by freezing-point depression (model 3W2, Advanced Instruments, Needham Heights, MA). Plasma AVP levels were measured by
radioimmunoassay, as described previously (12).
Acute oral water load. Acute oral water loads were performed in the glucocorticoid-deficient rats and the control rats to determine the effect of glucocorticoid deficiency on renal water excretion. The water load was studied 2 h after removal of food and water. The rats were given 30 ml/kg of deionized water by gastric tubes under light ether anesthesia. The animals were then placed in individual metabolic cages (Natsume, Tokyo, Japan) and allowed to awaken. Spontaneously voided urine samples were collected at 20-min intervals for 3 h. The final urine samples were obtained by gentle abdominal massage at the end of experiments. Urine volume and urinary osmolality (Uosm) were measured, and percent excretion water-loaded and basal and minimal Uosm were recorded. Uosm was measured by freezing-point depression.
A few days later, the acute oral water loads (30 ml/kg) were again carried out. On that occasion, the rats were killed by decapitation 1 h after the water loads. This was done because our previous studies showed that the maximal urine flow and minimal Uosm occurred 40-60 min after the oral water load (27, 33). Trunkal blood and both kidneys were obtained to determine plasma AVP levels and expressions of AQP2 mRNA and protein. The same experiments were performed in the glucocorticoid-deficient rats and the control rats receiving 30 mg/kg of the nonpeptide AVP V2-receptor antagonist 5-dimethylamino-1-[4-(2-methylbenzoylamino) benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine hydrochloride (OPC-31260; Otsuka Pharmaceutical, Osaka, Japan) (37). An acute oral water load was started 2 h after the oral administration of OPC-31260.Northern blot analysis.
The experimental procedure was performed by the modified method from
that described previously (5). Total cellular RNA from
whole kidneys was extracted by the acid guanidium
thiocyanate-phenol-chloroform method (3). Total RNA (20 µg) was denatured with formamide and formaldehyde at 65°C for 15 min, then electrophoresed on a 1% agarose-2.2 M formaldehyde gel, and
then blotted onto nylon membrane filters (Hybond-N+, Amersham,
Buckinghamshire, UK). The cDNA probes for rat AQP2 and -actin were
labeled with digoxigenin (DIG)-11-UTP by the random primed labeling
method (DIG DNA labeling kit, Roche, Tokyo, Japan). The filters were
hybridized at 42°C for at least 12 h with the probes. After
hybridization, the filters were washed twice in 2× saline sodium
citrate (SSC) and 0.1% SDS for 20 min at room temperature, and then
washed three times with 0.2× SSC and 0.1% SDS at 42°C. The filters
were incubated by chemiluminescent substrate (Tropix, Bedford, MA) and
exposed to Kodak X-Omat film (Eastman Kodak, Rochester, NY) for 4 h at 37°C. The films were analyzed by densitometry (CS-9000,
Shimadzu, Kyoto, Japan) to show the quantitative comparison. All the
data were calculated to show the ratio of density of AQP2 mRNA to that
of
-actin mRNA and further expressed as a percent increase in the
density compared with the density of control.
Western blot analysis. The expression of AQP2 protein in the kidney medulla was determined by Western blot analysis as described previously (28, 30). Membranes were prepared from rat kidney medulla by homogenization in a Potter Elvehjem apparatus. After homogenization in 10 vol of 0.32 M sucrose, 5 mM Tris · HCl, 2 mM EDTA, 0.1 mM phenylmethylsulfonyl fluoride, two centrifugations (1,000 g, 10 min) were applied. The supernatants were then centrifuged at 250,000 g for 30 min, and the pellets were suspended in the same buffer (membrane fraction). The samples were solubilized in a sample loading buffer; 3% SDS, 65 mM Tris · HCl, 10% glycerol, and 5% 2-mercaptoethanol, and heated at 70°C for 5 min. They were separated by SDS-PAGE by using 10% polyacrylamide gels and were transferred to polyvinyl membranes (Immobilon; Millipore, Bedford, MA). The blots were incubated with an antiserum (1:100 dilution) against 15 COOH-terminal synthetic peptides of rat AQP2 (Tyr0-AQP2 [V257-A271]). After rinsing, the blots were immersed with a 1:10,000 dilution of goat anti-rabbit horseradish peroxidase-conjugated antibodies. The blots were incubated with the enhanced chemiluminescence (ECL) substrate and exposed to Hyperfilm ECL to visualize the immunoreactive bands.
AVP receptor binding.
The experimental procedure was modified from the methods of Jard et al.
(14). Renal medullary tissues were homogenized in a
Potter-Elvehjen apparatus in 10 vol of homogenized solution (0.32 M
sucrose, 5 mM Tris · HCl, 2 mM EDTA, 0.1 mM phenylmethylsulfonyl fluoride). After the homogenization, the samples were centrifuged twice
at 1,000 g for 10 min at 4°C. The supernatants were then centrifuged at 250,000 g for 30 min at 4°C, and the
pellets were suspended in the ice-cold binding buffer [50 mM Tris
· HCl (pH 7.4), 5 mM MgCl2, 1 mg/ml bovine serum
albumin]. Two hundred microliters of the binding buffer containing
2 × 109 M [3H]AVP (specific activity,
67.6 Ci/mmol; New England Nuclear, Boston, MA) in the absence or
presence of cold AVP (1 × 10
9~1 × 10
6 M) were added to the tubes, and then the reaction was
initiated by the addition of the membrane fraction (100-200 µg)
at 4°C for 60 min. After the incubation, 3 ml of the ice-cold binding
buffer were added. The mixture was then filtered through glass
microfiber filters (Whatmen 2.4-cm GF/C; Whatman, Maidstone, UK). The
filters were rinsed three times with 3 ml of ice-cold binding buffer. They were put into counting vials, and 10 ml of scintillation solution
were added. The radioactivity was counted with a liquid scintillation
counter (model LSC-671, Aloka, Tokyo, Japan). Protein was measured by a
Bio-Rad protein assay kit.
Semiquantitative multiprimer RT-PCR.
Total RNA was isolated from whole kidney in the same manner as in
Northern blotting. Reverse transcription was performed by using a cDNA
synthesis kit (SuperScript Preamplification System for first-strand
cDNA synthesis, GIBCO-BRL, Life Technology, Rockville, MD). It was
carried out in a 20-µl reaction volume containing 5 µg total RNA, 6 µl of buffer, 1 µl of RNase inhibitor, 1 µl of deoxynucleotide
mixture, 5 µl of random primer, and 1 µl (200 U) of SuperScript.
Reaction tubes were incubated at 42°C for 50 min, and the reaction
was stopped by heating at 70°C for 15 min. Then the reaction tubes
were placed on ice until the addition of PCR reagents. PCR was carried
out by using 1 µl cDNA stock solution in the presence of 0.01U/µl
r-Taq enzyme (Takara, Otsu, Japan), 0.2 µM gene-specific
primer, 200 µM dNTPs, 10 mM Tris · HCl, 1.5 mM
MgCl2, 50 mM KCl, and 0.1% Triton X-100, and cycled 24 cycles (57°C for 30 s, 72°C for 5 min, 95°C for 60 s),
starting at 95°C for 1 min and finishing at 72°C for 5 min. The
gene-specific primers of AQP2 and -actin were made according to the
study of Yasui et al. (38). The primers of AQP2 were
5'-AGTGCTGGCTGAGTTCTTGG-3' (antisense) and 5'-GCTGTGGCGTTGTTGTGGAG-3'
(sense), those of AVP V2 receptors were
5'-CCTCCTACATGATCCTGGCCATGAG-3' (antisense) and
5'-TGCACCAGGAAGAAGGGTGCCCAGCA-3' (sense), and those of
-actin were
5'-TGAACCCTAAGGCCAACCGT-3' (antisense) and 5'-GCTAGGAGCCAGGGCAGTA-3' (sense). The product sizes of AQP2, V2 receptor, and
-actin were 344, 523, and 635 bp, respectively. Twenty microliters
of the PCR solution were separated on a 2% agarose gel and stained
with ethidium bromide. Each RT-PCR product was subjected to
restriction-enzyme analysis to verify the specificity (data not shown).
When the RTase was omitted from the RT reaction solution, no products
appeared, confirming that the products were produced from mRNA and not
contaminating genomic DNA. All semiquantitative multiprimer (SQM)
RT-PCRs were made at least three times with three different RNA
preparations. All reaction solutions (except RNA and enzymes) in the
SQM RT-PCR were premixed to eliminate errors during pipetting. The
Hi-Lo DNA Marker (Abetec, Tokyo, Japan) was used on all agarose gels as
a molecular weight marker.
Statistical analysis.
Values of percent excretion water loaded, Uosm, serum
sodium, Posm, plasma AVP levels, ratio of the density of
AQP2 mRNA expression to that of -actin mRNA, and density of AQP2
protein in immunoreactive bands were analyzed by Student's
t-test. A P value of <0.05 was considered significant.
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RESULTS |
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Serum sodium levels were 139.3 ± 0.3 meq/l in the
glucocorticoid-deficient rats, a value less than that of 146.5 ± 0.8 meq/l in the control rats (n = 6, P < 0.05). Figure 1 shows the expression of AQP2 mRNA and protein in the kidney of the glucocorticoid-deficient and the control rats. A transcript at 1.5 kb was seen in both rats,
which expresses AQP2 mRNA (Fig. 1A). Also, a 4.4-kb
transcript was detected, that is, alternative splicing or
polyadenylation variants, as described previously (6,
30). The expression of AQP2 mRNA increased by 164.2 ± 3.7% in the glucocorticoid-deficient rats, compared with the
control rats (n = 6, P < 0.01 ).
Similar results were obtained with AQP2 protein in Western blot
analysis (Fig. 1B). Immunoblots showed the bands at 29 and
36-45 kDa. High-molecular-weight-mass band of 36-45 kDa was
the glycosylated form of AQP2 protein (30). Also, the
densitometric analysis showed that the glucocorticoid-deficient rats
had increased AQP2 protein in renal medulla by 137.2 ± 5.8% compared with that of the control rats (n = 6, P < 0.05).
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Table 1 shows the results of an acute
oral water load test. Percent excretion water loaded was 38.7 ± 11.7% in the glucocorticoid-deficient rats, which was less than that
of 139.3 ± 10.1% in the control rats (n = 6, P < 0.01). The glucocorticoid-deficient rats had impaired water excretion. The minimal Uosm in the
glucocorticoid-deficient rats was as high as 379.4 ± 50.8 mosmol/kgH2O, a value significantly greater than that of
138.0 ± 25.5 mosmol/kgH2O in the control rats
(P < 0.01). The administration of 30 mg/kg OPC-31260
totally restored the impairment in water excretion in the
glucocorticoid-deficient rats, as the percent excretion water loaded
was 137.5 ± 10.0% and the minimal Uosm 83.6 ± 7.0 mosmol/kgH2O. The plasma AVP level was 2.6 ± 0.8 pg/ml in the glucocorticoid-deficient rats allowed free access to water
and was reduced to only 1.4 ± 0.1 pg/ml 60 min after the oral
water load. In the control rats this maneuver decreased plasma AVP
levels from 2.9 ± 0.5 to 1.2 ± 0.1 pg/ml.
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The expression of AQP2 mRNA and protein 1 h after an acute oral
water load in the glucocorticoid-deficient rats is shown in Fig.
2. The expression of AQP2 mRNA was still
increased in the glucocorticoid-deficient rats, compared with that in
the control (Fig. 2A). The desitometric analysis revealed a
141.5 ± 17.3% increase in the AQP2 mRNA expression in the
glucocorticoid-deficient rats (n = 6, P < 0.05). When the study was carried out in the rats receiving 30 mg/kg
OPC-31260, an increase in the expression of AQP2 mRNA totally
disappeared in the glucocorticoid-deficient rats (89.3 ± 8.8%,
n = 6). This finding was in concert with the marked
water diuresis as shown in Table 1. Similar results were obtained by
the Western blotting, as shown in Fig. 2B. A 29-kDa protein
increased in the glucocorticoid-deficient rats, compared with the
control. Densitometric analysis resulted in a 120.3 ± 6.8%
increment in AQP2 protein (n = 6, P < 0.05). The administration of OPC-31260 completely abolished the
increase in AQP2 protein in the glucocorticoid-deficient rats.
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Membrane fraction was prepared from the kidney medulla of the
glucocorticoid-deficient and the control rats to determine whether glucocorticoid deficiency affects [3H]AVP receptor
binding. Figure 3 shows a Scatchard
analysis of AVP receptor binding. The equilibrium dissociation constant
(Kd) was 1.51 × 1010 and
1.75 × 10
10 M in the control and the
glucocorticoid-deficient rats, respectively. The maximal binding
capacity (Bmax) was 8.45 and 7.29 pmol/mg protein in the
control and the glucocorticoid-deficient rats, respectively. There was
no difference in Kd and Bmax between
the two groups of rats.
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The expression of AVP V2 receptor mRNA and AQP2 mRNA
analyzed by SQM RT-PCR in the glucocorticoid-deficient rats is shown in
Fig. 4. The expression of AQP2 mRNA in
the glucocorticoid-deficient rats was higher than that of control rats.
The densitometric analysis revealed a 140.3 ± 9.5% increase in
the glucocorticoid-deficient rats (n = 6, P < 0.05), which was in concert with the study in Northern blot described earlier. In contrast, the expression of AVP
V2 receptor mRNA seemed likely to be somewhat high in the glucocorticoid-deficient rats compared with the control rats, but there
was no significance between the control and the
glucocorticoid-deficient rats.
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DISCUSSION |
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Impaired water excretion occurs in patients with hypopituitarism and isolated ACTH deficiency and experimental models of glucocorticoid deficiency (1, 7, 11, 13, 15, 17, 22, 25, 31, 32). In this pathological setting there is hyponatremia to various extents. Nonsuppressible release of AVP is found despite hypoosmolality, which should suppress AVP release to undetectable levels in humans and rats (1, 8, 11, 13, 17, 21). In addition, a study performed in adrenalectomized homozygous Brattleboro rats showed that AVP-independent factors are involved in the impaired water excretion associated with glucocorticoid deficiency (7). Almost two decades ago we demonstrated that the AVP V2-receptor antagonist promptly normalized renal water excretion in the experimental rats with glucocorticoid deficiency (13). Also, it is evident that the defect in renal water excretion could be corrected by replacement of glucocorticoid hormone in these animals and patients (7, 11, 13, 15). Therefore, nonsuppressible secretion of AVP plays a crucial role in impaired water excretion in glucocorticoid deficiency.
In the present study we confirmed impaired renal water excretion in the glucocorticoid-deficient rats. The percent excretion water loaded was reduced to 38.7% (mean), and the minimal Uosm remained as high as 379.4 mosmol/kgH2O (mean). These values were markedly different from those in the control rats. The radioimmunoassayable plasma levels of AVP were high compared with the Posm in the glucocorticoid-deficient rats. Plasma AVP levels were not sufficiently suppressed by an acute oral water load in the glucocorticoid-deficient rats, which suppressed plasma AVP levels to 1.2 ± 0.1 pg/ml in the control. As indicated the impairment in water excretion, the expression of AQP2 mRNA and protein in kidney was significantly increased in the glucocorticoid-deficient rats compared with the control. The enhanced expression of AQP2 mRNA and protein totally disappeared in the glucocorticoid-deficient rats after receiving the AVP V2-receptor antagonist, in association with the normalization of water excretion. This finding strongly indicates that the augmentation in AQP2 mRNA expression is dependent on plasma AVP. In addition, urinary excretion of AQP2 is exaggerated in the patients with hypopituitarism, particularly in hypofunction of the pituitary-adenocortical axis (27). Because ~3% of AQP2 in renal collecting duct cells is excreted into the urine (23), and urinary excretion of AQP2 positively correlates with plasma AVP levels (29), urinary AQP2 excretion allows for an understanding of AVP dependency. Upregulation of AQP2 mRNA expression in kidney was evident in the glucocorticoid-deficient rats, which could be tightly linked with exaggerated urinary excretion of AQP2 in the pituitary-adenocortical dysfunction. Such an upregulation is also found in other pathological states of impaired water excretion, including the syndrome of inappropriate secretion of antidiuretic hormone, liver cirrhosis with ascites, and congestive heart failure (2, 5, 20, 35).
What mechanisms underlie in the upregulation of AQP2 mRNA expression in the glucocorticoid-deficient rats? Augmented antidiuresis has been understood as dependent on nonsuppressible levels of plasma AVP compared with hypoosmolality, though plasma AVP levels are not so high, in most settings of water retention (12, 13, 27, 33). An information of the augmentation could be simply accepted by the kidney. If so, how does the kidney distinguish such nonsuppressible levels of plasma AVP from those under normal regulation? As a result, the exaggerated action of AVP is found. We examined [3H]AVP receptor binding in the glucocorticoid-deficient rats. Bmax was ~14% less than that in the control, although it was not significantly different. Kd values were almost equal in these two groups. The expression of AVP V2 receptor mRNA was somewhat stimulated in the glucocorticoid-deficient rats, which might be due to the decrease in receptor numbers. Therefore, at the receptor site the initiation of intracellular signaling is kept in the normal range under the chronically relative AVP excess condition. In the literature, chronic treatment with small amounts of dDAVP for a few days in rats, which did not induce short-term desensitization, increased AVP-induced cAMP production by 30% (24). In the present study, it is clear that the expression of AQP2 mRNA was upregulated in the glucocorticoid-deficient rats. Chronically nonsuppressible levels of plasma AVP do not always downregulate the V2 receptor function and could rather maintain its long-term stimulation on V2 receptor-mediated signaling. In patients with impaired water excretion, the exaggerated urinary excretion of AQP2 was more marked and seemed likely to be dissociated from the positive correlation between urinary excretion of AQP2 and plasma AVP levels in the normal subjects (27). Renal action of AVP is more manifest than that expected from the plasma AVP levels despite hypoosmolality in the patients with impaired water excretion. However, there is no evidence that other factors except for AVP are involved in regulation of AQP2 in renal collecting duct cells. These findings cannot rule out the unknown mechanism for enhancing postreceptor signaling of AVP. Further study will be necessary to elucidate the existence of an enhancer system in the upregulation of AQP2 in pathological state of impaired water excretion, including glucocorticoid deficiency.
In conclusion, we demonstrated impaired water excretion in glucocorticoid-deficient rats. Nonsuppressible release of AVP was found despite hypoosmolality. The expression of AQP2 mRNA and protein was upregulated, and the AVP V2-receptor antagonist totally abolished the increases in their expression. AVP V2 receptor binding capacity and its mRNA expression were maintained. The AQP2 mRNA expression was more manifest in the kidney than that expected from the plasma AVP levels. These results indicate that the upregulation of AQP2 plays a crucial role in impaired water excretion, dependent on AVP, in glucocorticoid deficiency.
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ACKNOWLEDGEMENTS |
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The present study was supported by grants from the Ministry of Education, Science, and Culture of Japan (no. 10770557). A portion of this study was presented at the 81st Annual Meeting of The Endocrine Society in San Diego, CA, June 12-15, 1999.
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FOOTNOTES |
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Address for reprint requests and other correspondence: S. Ishikawa, Div. of Endocrinology and Metabolism, Dept. of Medicine, Jichi Medical School, 3311-1 Yakushiji Minamikawachi-machi, Tochigi 329-0498, Japan (E-mail : saneiskw{at}jichi.ac.jp).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Received 14 July 1999; accepted in final form 7 April 2000.
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REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
1.
Amhed, AB,
George BC,
Gonzalez-Auvert T,
and
Dingman JF.
Increased plasma arginine vasopressin in clinical adrenocortical insufficiency and its inhibition of glucocorticoids.
J Clin Invest
46:
111-123,
1967[ISI][Medline].
2.
Asahina, Y,
Izumi N,
Enomoto N,
Sasaki S,
Fushimi K,
Marumo F,
and
Sato C.
Increased gene expression of water channel in cirrhotic rat kidneys.
Hepatology
21:
169-173,
1995[ISI][Medline].
3.
Chomczynski, P,
and
Sacchi N.
Single-step method of RNA isolation by acid guanidium thiocyanate-phenol-chloroform extraction.
Anal Biochem
162:
156-159,
1987[ISI][Medline].
4.
Doucet, A,
Barlet-Bas C,
Siaume-Perez S,
Khadouri C,
and
Marsy S.
Gluco- and mineralocorticoids control adenylate cyclase in specific nephron segments.
Am J Physiol Renal Fluid Electrolyte Physiol
258:
F812-F820,
1990
5.
Fujita, N,
Ishikawa S,
Sasaki S,
Fujisawa G,
Fushimi K,
Marumo F,
and
Saito T.
Role of water channel AQP-CD in water retention in SIADH and cirrhotic rats.
Am J Physiol Renal Fluid Electrolyte Physiol
269:
F926-F931,
1995
6.
Fushimi, K,
Uchida S,
Hara Y,
Hirata Y,
Marumo F,
and
Sasaki S.
Cloning and expression of apical membrane water channel of rat kidney collecting duct tubule.
Nature
361:
549-552,
1993[ISI][Medline].
7.
Green, HH,
Harrington AR,
and
Valtin H.
On the role of antidiuretic hormone in the inhibition of acute water diuresis in adrenal insufficiency and the effects of gluco-and mineralocorticoids in reversing the inhibition.
J Clin Invest
49:
1724-1736,
1970[ISI][Medline].
8.
Herman, JP.
In situ hybridization analysis of vasopressin gene transcription in the paraventricular and supraoptic nuclei of the rat: regulation by stress and glucocorticoids.
J Comp Neurol
363:
15-27,
1995[ISI][Medline].
9.
Hozawa, S,
Holtzman EJ,
and
Ausiello DA.
cAMP motifs regulating transcription in the aquaporin-2 gene.
Am J Physiol Cell Physiol
270:
C695-C702,
1996.
10.
Ishikawa, S.
Cellular action of arginine vasopressin in the kidney.
Endocr J
40:
373-386,
1993[ISI][Medline].
11.
Ishikawa, S,
Fujisawa G,
Tsuboi Y,
Okada K,
Kuzuya T,
and
Saito T.
Role of antidiuretic hormone in hyponatremia in patients with isolated adrenocorticotropic hormone deficiency.
Endocrinol Jpn
38:
325-330,
1991[Medline].
12.
Ishikawa, S,
Saito T,
Okada K,
Tsutsui K,
and
Kuzuya T.
Effect of vasopressin antagonist on water excretion in inferior vena cava constriction.
Kidney Int
30:
49-55,
1986[ISI][Medline].
13.
Ishikawa, S,
and
Schrier RW.
Effect of arginine vasopressin antagonist on renal water excretion in glucocorticoid and mineralocorticoid deficient rats.
Kidney Int
22:
587-593,
1982[ISI][Medline].
14.
Jard, S,
Lombard C,
Marie J,
and
Devilliers G.
Vasopressin receptors from cultured mesangial cells resemble V1a type.
Am J Physiol Renal Fluid Electrolyte Physiol
253:
F41-F49,
1987
15.
Kamoi, K,
Tamura T,
Tanaka K,
Ishibashi M,
and
Yamaji T.
Hyponatremia and osmoregulation of thirst and vasopressin secretion in patients with adrenal insufficiency.
J Clin Endocrinol Metab
77:
1584-1588,
1993[Abstract].
16.
Knepper, MA,
and
Rector FC, Jr.
Urinary concentration and dilution.
In: The Kidney, edited by Brenner BM,
and Rector FC, Jr.. Philadelphia, PA: Saunders, 1995, p. 532-570.
17.
Linas, SL,
Berl T,
Robertson GL,
Aisenbrey GA,
Schrier RW,
and
Anderson RJ.
Role of vasopressin in the impaired water excretion of glucocorticoid deficiency.
Kidney Int
18:
58-67,
1980[ISI][Medline].
18.
Matsumura, Y,
Uchida S,
Furuno M,
Marumo F,
and
Sasaki S.
Cyclic AMP and hypertonicity increase AQP-2 transcription through their responsive element.
J Am Soc Nephrol
8:
861-867,
1997[Abstract].
19.
Nielsen, S,
DiGiovanni SR,
Christensen EI,
Knepper MA,
and
Harris HW.
Cellular and subcellular immunolocalization of vasopressin-regulated water channel in rat kidney.
Proc Natl Acad Sci USA
90:
11663-11667,
1993[Abstract].
20.
Nielsen, S,
Terris J,
Andersen D,
Ecelbarger C,
Frokler J,
Jonassen T,
Marples D,
Knepper MA,
and
Peterson JS.
Congestive heart failure in rats is associated with increased expression and targeting of aquaporin-2 water channel in collecting duct.
Proc Natl Acad Sci USA
94:
5450-5455,
1997
21.
Pyo, HJ,
Summer SN,
Kim JK,
and
Schrier RW.
Vasopressin gene in glucocorticoid hormone-deficient rats.
Ann NY Acad Sci
689:
659-662,
1993[ISI][Medline].
22.
Raff, H.
Glucocorticoid inhibition of neurohypophysial vasopressin secretion.
Am J Physiol Regulatory Integrative Comp Physiol
252:
R635-R644,
1987
23.
Rai, T,
Sekine K,
Kanno K,
Hata K,
Miura M,
Mizushima A,
Marumo F,
and
Sasaki S.
Urinary excretion of aquaporin -2 water channel protein in human and rat.
J Am Soc Nephrol
8:
1357-1362,
1997[Abstract].
24.
Rajerison, RM,
Butlen D,
and
Jard S.
Effects of in vivo treatment with vasopressin and analogs on renal adenylate cyclase responsiveness to vasopressin stimulation in vitro.
Endocrinology
101:
1-12,
1977[ISI][Medline].
25.
Robinson, AG,
Seif SM,
Verbalis JG,
and
Brownstein MJ.
Quantitation of changes in the content of neurohypophyseal peptides in hypothalamic nuclei after adrenalectomy.
Neuroendocrinology
36:
347-350,
1983[ISI][Medline].
26.
Sabolic, I,
Katsura T,
Verbavatz J-M,
and
Brown D.
The AQP-2 water channel: effect of vasopressin treatment, microtubule disruption, and distribution in neonatal rats.
J Membr Biol
143:
165-175,
1995[ISI][Medline].
27.
Saito, T,
Ishikawa S,
Ando F,
Okada N,
Nakamura T,
Kusaka I,
Higashiyama M,
Nagasaka S,
and
Saito T.
Exaggerated urinary excretion of aquaporin-2 in the pathological state of impaired water excretion dependent upon arginine vasopressin.
J Clin Endocrinol Metab
83:
4034-4040,
1998
28.
Saito, T,
Ishikawa S,
Sasaki S,
Fujita N,
Fushimi K,
Okada N,
Takeuchi K,
Sakamoto A,
Oogawara S,
Kaneko T,
Marumo F,
and
Saito T.
Alteration in water channel AQP-2 by removal of AVP stimulation in collecting duct cells of dehydrated rats.
Am J Physiol Renal Physiol
272:
F183-F191,
1997
29.
Saito, T,
Ishikawa S,
Sasaki S,
Nakamura T,
Rokkaku K,
Kawakami A,
Honda K,
Marumo F,
and
Saito T.
Urinary excretion of aquaporin-2 in the diagnosis of central diabetes insipidus.
J Clin Endocrinol Metab
82:
1823-1827,
1997
30.
Sasaki, S,
Fushimi K,
Saito H,
Saito F,
Uchida S,
Ishibashi K,
Kuwahara M,
Ikeuchi T,
Inui K,
Nakajima K,
Watanabe T,
and
Marumo F.
Cloning, characterization and chromosomal mapping of human aquaporin of collecting duct.
J Clin Invest
93:
1250-1256,
1994[ISI][Medline].
31.
Seif, SM,
Robinson AG,
Zimmerman EA,
and
Wilkins J.
Plasma neurophysin and vasopressin in the rat: response to adrenalectomy and steroid replacement.
Endocrinology
103:
1009-1015,
1978[Abstract].
32.
Slessor, A.
Studies concerning the mechanism of water retention in Addison's disease and in hypopituitarism.
J Clin Endocrinol
11:
700-723,
1951.
33.
Tsuboi, Y,
Ishikawa S,
Fujisawa G,
Okada K,
and
Saito T.
Therapeutic efficacy of non-peptide AVP antagonist OPC-31260 in cirrhotic rats.
Kidney Int
46:
237-244,
1994[ISI][Medline].
34.
Uchida, S,
Sasaki S,
Fushimi K,
and
Marumo F.
The isolation of human aquaporin-CD gene.
J Biol Chem
269:
23451-23455,
1994
35.
Xu, DL,
Martin PY,
Ohara M,
John JS,
Pattison T,
Meng X,
Morris K,
Kim JK,
and
Schrier RW.
Upregulation of aquaporin-2 water channel expression in chronic heart failure rat.
J Clin Invest
99:
1500-1505,
1997
36.
Yamamoto, T,
Sasaki S,
Fushimi K,
Ishibashi K,
Yaoita E,
Kawasaki K,
Marumo F,
and
Kihara I.
Vasopressin increases AQP-CD water channel in apical membrane of collecting duct cells in Brattleboro rats.
Am J Physiol Cell Physiol
268:
C1546-C1551,
1995
37.
Yamamura, Y,
Ogawa H,
Yamashita H,
Chihara T,
Miyamoto H,
Nakamura S,
Onogawa T,
Yamashita T,
Hosokawa T,
Mori T,
Tominaga M,
and
Yabuuchi Y.
Characterization of a novel aquauretic agent, OPC-31260 as an orally effective, nonpeptide vasopressin V2 receptor antagonist.
Br J Pharmacol
105:
787-791,
1992[Abstract].
38.
Yasui, M,
Marples D,
Belusa R,
Eklof AC,
Celsi G,
Nielsen S,
and
Aperia A.
Development of urinary concentrating capacity: role of aquaporin-2.
Am J Physiol Renal Fluid Electrolyte Physiol
271:
F461-F468,
1996