scholarly journals Updates and Perspectives on Aquaporin-2 and Water Balance Disorders

2021 ◽  
Vol 22 (23) ◽  
pp. 12950
Author(s):  
Yumi Noda ◽  
Sei Sasaki
Keyword(s):  
Water Balance ◽  
Antidiuretic Hormone ◽  
Water Retention ◽  
Hormone Secretion ◽  
The Body ◽  
Water Reabsorption ◽  
Balance Disorders ◽  
Aquaporin 2 ◽  
Vasopressin V2 Receptor ◽  
V2 Receptor

Ensuring the proper amount of water inside the body is essential for survival. One of the key factors in the maintenance of body water balance is water reabsorption in the collecting ducts of the kidney, a process that is regulated by aquaporin-2 (AQP2). AQP2 is a channel that is exclusively selective for water molecules and impermeable to ions or other small molecules. Impairments of AQP2 result in various water balance disorders, including nephrogenic diabetes insipidus (NDI), which is a disease characterized by a massive loss of water through the kidney and consequent severe dehydration. Dysregulation of AQP2 is also a cause of water retention with hyponatremia in heart failure, hepatic cirrhosis, and syndrome of inappropriate antidiuretic hormone secretion (SIADH). Antidiuretic hormone vasopressin is an upstream regulator of AQP2. Its binding to the vasopressin V2 receptor promotes AQP2 targeting to the apical membrane and thus enables water reabsorption. Tolvaptan, a vasopressin V2 receptor antagonist, is effective and widely used for water retention with hyponatremia. However, there are no studies showing improvement in hard outcomes or long-term prognosis. A possible reason is that vasopressin receptors have many downstream effects other than AQP2 function. It is expected that the development of drugs that directly target AQP2 may result in increased treatment specificity and effectiveness for water balance disorders. This review summarizes recent progress in studies of AQP2 and drug development challenges for water balance disorders.

scholarly journals Vasopressin–aquaporin-2 pathway: recent advances in understanding water balance disorders

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 149 ◽  
Author(s):  
Marianna Ranieri ◽  
Annarita Di Mise ◽  
Grazia Tamma ◽  
Giovanna Valenti
Keyword(s):  
Water Balance ◽  
Collecting Duct ◽  
Hormone Secretion ◽  
Polycystic Kidney ◽  
Balance Disorders ◽  
Inappropriate Antidiuretic Hormone Secretion ◽  
Aquaporin 2 ◽  
Therapeutic Benefits ◽  
Recent Advances ◽  
Autosomal Dominant Polycystic Kidney

The alteration of water balance and related disorders has emerged as being strictly linked to the state of activation of the vasopressin–aquaporin-2 (vasopressin–AQP2) pathway. The lack of responsiveness of the kidney to the vasopressin action impairs its ability to concentrate the urine, resulting in polyuria, polydipsia, and risk of severe dehydration for patients. Conversely, non-osmotic release of vasopressin is associated with an increase in water permeability in the renal collecting duct, producing water retention and increasing the circulatory blood volume. This review highlights some of the new insights and recent advances in therapeutic intervention targeting the dysfunctions in the vasopressin–AQP2 pathway causing diseases characterized by water balance disorders such as congenital nephrogenic diabetes insipidus, syndrome of inappropriate antidiuretic hormone secretion, nephrogenic syndrome of inappropriate antidiuresis, and autosomal dominant polycystic kidney disease. The recent clinical data suggest that targeting the vasopressin–AQP2 axis can provide therapeutic benefits in patients with water balance disorders.

scholarly journals Vasopressin-vermittelte Wasserrückresorption im Sammelrohr der Niere

BIOspektrum ◽  
2021 ◽  
Vol 27 (2) ◽  
pp. 165-167
Author(s):  
Sandrine Baltzer ◽  
Enno Klussmann
Keyword(s):  
Water Balance ◽  
Small Molecules ◽  
High Throughput ◽  
Molecular Mechanisms ◽  
Collecting Duct ◽  
Water Channel ◽  
Water Reabsorption ◽  
Balance Disorders ◽  
Water Homeostasis ◽  
Balance Disorder

AbstractVasopressin-mediated water reabsorption from primary urine in the renal collecting duct is essential for regulating body water homeostasis and depends on the water channel aquaporin-2 (AQP2).Dysregulation of the process can cause water balance disorders. Here, we present cell-based high-throughput screenings to identify proteins and small molecules as tools to elucidate molecular mechanisms underlying the AQP2 control and as potential starting points for the development of water balance disorder drugs.

scholarly journals Nephrogenic Syndrome of Inappropriate Antidiuresis

2012 ◽  
Vol 2012 ◽  
pp. 1-4 ◽  
Author(s):  
D. Morin ◽  
J. Tenenbaum ◽  
B. Ranchin ◽  
T. Durroux
Keyword(s):  
Phenotypic Variability ◽  
Receptor Gene ◽  
Hormone Secretion ◽  
Fluid Restriction ◽  
Missense Mutations ◽  
Loss Of Function ◽  
Vasopressin V2 Receptor ◽  
V2 Receptor ◽  
V2 Receptor Gene ◽  
Inappropriate Antidiuresis

Mutations in the vasopressin V2 receptor gene are responsible for two human tubular disorders: X-linked congenital nephrogenic diabetes insipidus, due to a loss of function of the mutant V2 receptor, and the nephrogenic syndrome of inappropriate antidiuresis, due to a constitutive activation of the mutant V2 receptor. This latter recently described disease may be diagnosed from infancy to adulthood, as some carriers remain asymptomatic for many years. Symptomatic children, however, typically present with clinical and biological features suggesting inappropriate antidiuretic hormone secretion with severe hyponatremia and high urine osmolality, but a low plasma arginine vasopressin level. To date, only two missense mutations in the vasopressin V2 receptor gene have been found in the reported patients. The pathophysiology of the disease requires fuller elucidation as the phenotypic variability observed in patients bearing the same mutations remains unexplained. The treatment is mainly preventive with fluid restriction, but urea may also be proposed.

Administration of oxytocin affects vasopressin V2 receptor and aquaporin-2 gene expression in the rat

Life Sciences ◽  
1999 ◽  
Vol 64 (16) ◽  
pp. 1447-1453 ◽  
Author(s):  
Yasuhiro Terashima ◽  
Kunikazu Kondo ◽  
Yutaka Oiso
Keyword(s):  
Gene Expression ◽  
Aquaporin 2 ◽  
Vasopressin V2 Receptor ◽  
V2 Receptor

EFFECTS OF DEOXYCORTICOSTERONE ACETATE AND CORTISONE ON THE EXCRETION OF HYPOTONIC SALINE BY ADRENALECTOMIZED RATS

1954 ◽  
Vol 11 (3) ◽  
pp. 261-268 ◽  
Author(s):  
D. F. COLE
Keyword(s):  
Antidiuretic Hormone ◽  
Hormone Secretion ◽  
The Body ◽  
Renal Tubules ◽  
Water Diuresis ◽  
Deoxycorticosterone Acetate ◽  
Water Excretion ◽  
Normal Water ◽  
Hypotonic Saline ◽  
Adrenalectomized Rats

SUMMARY The response to loads of hypotonic saline has been investigated in intact and in adrenalectomized rats treated with deoxycorticosterone acetate, with cortisone acetate and with both steroids. The response of untreated adrenalectomized animals was also studied. Intact rats excreted more water than sodium during the 5 hr after loading with hypotonic saline. There was a reduction of the proportion of water reabsorbed in the renal tubules, but the proportion of sodium reabsorbed was unaltered. Adrenalectomized rats, either with or without deoxycorticosterone treatment, did not show this diuretic response, and there was evidence that sodium was lost from the body cells. Rats in these two groups reabsorbed a smaller proportion of sodium in their renal tubules than intactrats. Adrenalectomized rats treated with cortisone showed partial restoration of the ability to excrete water, but the renal loss of sodium was greater than in intact animals. Treatment of adrenalectomized rats with both cortisone and deoxycorticosterone restored water excretion to normal values, but excessive amounts of sodium were lost. In neither group which received cortisone was there any indication of loss of cell sodium. The response of rats in the group receiving both steroids was not a normal water diuresis because the animals were unable to excrete water without loss of sodium. It appeared unlikely that there was excessive antidiuretic hormone activity in the rats receiving cortisone and that some factor other than reduction of pituitary antidiuretic hormone secretion was essential for normal water diuresis.

Effects of DDAVP and AVP on sodium and water balance in conscious rat

1982 ◽  
Vol 243 (5) ◽  
pp. R512-R519 ◽  
Author(s):  
P. A. Gross ◽  
R. J. Anderson
Keyword(s):  
Water Balance ◽  
Arginine Vasopressin ◽  
Water Retention ◽  
Free Water ◽  
Physiological Adaptation ◽  
Sodium Balance ◽  
Water Reabsorption ◽  
Conscious Rat ◽  
Hypotonic Fluid ◽  
Sodium And Water Balance

Many aspects of the physiological adaptation to chronic vasopressin and hypotonic fluid administration remain unclear. We therefore infused vasopressin [either 1-desamino-8-D-arginine vasopressin (DDAVP) at 0.112 ng/h or arginine vasopressin (AVP) at 2.4 mU/h] and hypotonic fluid (0.22% NaCl at 3.1 ml/h) into conscious unrestrained rats for 4–6 days. To determine if a decrease in the hydrosmotic effect of vasopressin occurred, urinary osmolality, flow rate, and free water reabsorption were measured sequentially in vasopressin-treated and control animals (receiving 0.22% NaCl alone). Progressive increases in urine flow and decreases in urine osmolality and free water reabsorption occurred in vasopressin-treated animals. This decreased hydrosmotic effect was noted with both DDAVP and AVP and could be dissociated from hormonal degradation and urinary prostaglandin E2 excretion. Sodium and water balance were measured to assess the determinants of the hypotonic state following chronic vasopressin and hypotonic fluid. In DDAVP-treated animals, sodium balance remained constant and hyponatremia resulted from water retention alone. In AVP-treated animals, a greater degree of hyponatremia was observed and resulted from combined positive water balance and negative sodium balance. The difference in sodium balance observed when DDAVP- and AVP-treated animals were compared could not be attributed to differences in either magnitude of water retention or filtered load of sodium.

scholarly journals Effect of exogenous glucocorticoid on osmotically stimulated antidiuretic hormone secretion and on water reabsorption in man

2006 ◽  
Vol 155 (6) ◽  
pp. 845-848 ◽  
Author(s):  
Volker Bähr ◽  
Norma Franzen ◽  
Wolfgang Oelkers ◽  
Andreas F H Pfeiffer ◽  
Sven Diederich
Keyword(s):  
Antidiuretic Hormone ◽  
Water Deprivation ◽  
Hormone Secretion ◽  
Water Reabsorption ◽  
Glucocorticoid Treatment ◽  
Osmotic Stimulation ◽  
Before And After ◽  
Stimulation Of

Objective: Glucocorticoids exert tonic suppression of antidiuretic hormone (ADH) secretion. Hypocortisolism in secondary adrenocortical insufficiency can result in a clinical picture similar to the syndrome of inappropriate ADH secretion. On the other hand, in vitro and in vivo results provide evidence for ADH suppression in states of hypercortisolism. To test the hypothesis that ADH suppression is of relevance during glucocorticoid therapy, we investigated the influence of prednisolone on the osmotic stimulation of ADH. Design and methods: Seven healthy men were subjected to water deprivation tests with the measurement of plasma ADH (pADH) and osmolality (posmol) before and after glucocorticoid treatment (5 days 30 mg prednisolone per day). Results: Before glucocorticoid treatment, the volunteers showed a normal test with an adequate increase of pADH (basal 0.54 ± 0.2 to 1.9 ± 0.72 pg/ml (mean ± S.D.)) in relation to posmol(basal 283.3 ± 8.5 to 293.7 ± 6 mosmol/kg). After prednisolone intake, pADH was attenuated (<0.4 pg/ml) in spite of an increase of posmol from 289.3 ± 3.6 to 297.0 ± 5.5 mosmol/kg. However, urine osmolar concentration increased normally during water deprivation after prednisolone. Urinary cAMP excretion increased during water deprivation without glucocorticoid treatment from 3.56 ± 0.55 to 6.07 ± 0.76 μmol/l, reflecting the increased pADH levels. The rise in cAMP excretion was completely blunted by prednisolone treatment. Conclusions: We speculate that there may be an ADH-independent stimulation of the formation or function of aquaporin-2 channels by prednisolone and/or a direct osmotic stimulation of water reabsorption independent of ADH and glucocorticoid control.

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