Molecular analysis of impaired urinary diluting capacity in glucocorticoid deficiency

Wang, Weidong; Li, Chunling; Summer, Sandra N.; Falk, Sandor; Cadnapaphornchai, Melissa A.; Chen, Yung‐Chang; Schrier, Robert W.

doi:10.1152/ajprenal.00356.2005

Cited by 31 publications

(20 citation statements)

References 25 publications

(33 reference statements)

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“…The resultant decrease in stretch on the arterial baroreceptors in the carotid sinus and aortic arch removes the tonic vagal and glossopharyngeal inhibition on the central release of AVP. Elevated plasma AVP concentrations have been demonstrated in glucocorticoid-deficient animals (33,35) and patients with hypopituitarism (36) despite a degree of hyposmolality that would maximally suppress AVP in normal individuals. The messenger RNA for AVP in the hypothalamus also has been shown to be increased during glucocorticoid deficiency (37).…”

Section: Addison's Disease and Hypopituitarismmentioning

confidence: 99%

Body Water Homeostasis

Schrier¹

2006

Journal of the American Society of Nephrology

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T he discovery of the aquaporin-1 (AQP1) water channel by Agre and colleagues (1,2), which led to the Nobel Prize in 2003, has revolutionized the understanding of body fluid water regulation by the kidney. Moreover, the identification of other water channels in the kidney, namely AQP2, 3, and 4, along with urea and ion transporters, has allowed a much improved understanding of urinary dilution and concentration in health and disease at the cellular and molecular levels (3-8).The AQP have provided a pathway for water movement across cellular membranes that could not be explained by simple diffusion through the lipid bilayers of cell membranes. AQP1 has been found to be expressed constitutively on both the apical and the basolateral membranes of the proximal tubule and descending limb of Henle's loop. This water channel is not under control of vasopressin but is important in urinary concentration. Water efflux through these channels in the descending limb is an important factor in the countercurrent concentrating mechanism, and diminished maximal urinary osmolality has been shown in AQP1 knockout mice (9) and humans without the AQP1 gene (10).AQP2, 3, and 4 are expressed in the cortical and medullary collecting duct ( Figure 1) (11). AQP2 is found exclusively in the principal cells of the collecting tubule and collecting duct and is known to be regulated by arginine vasopressin (AVP). AQP3 and 4 are located on the basolateral membrane of the principal cells in the collecting duct. AQP3 knockout mice exhibit substantial polyuria secondary to vasopressin-resistant nephrogenic diabetes insipidus (NDI) (12). AQP3 is regulated by AVP. AQP4 predominates on the basolateral membrane of the inner medulla and is not regulated by AVP. AQP4 knockout mice also exhibit an NDI that is less severe than that observed in the AQP3 knockout mice (13). Whereas AQP3 and AQP4 constitute the exit channels for water movement across the basolateral membrane of the collecting duct, AQP2 is the water channel for water reabsorption across the apical membrane of the principal cells of the collecting duct. These transgenic mouse models of AQP deletion/mutation are of importance not only for kidney function but also for other epithelia (14).AVP regulates AQP2 in both an acute (short term) (15) and chronic (long term) manner (16,17). The short-term regulation by AVP involves trafficking of vesicles that contain AQP2 to the apical membrane with resultant increased water permeability. Suppression of plasma AVP reverses this exocytosis of AQP2, and the vesicles are retrieved from the membrane (endocytosis) into the cytoplasm. Both the short-and long-term regulation of AQP2 by AVP is initiated by activation of the V2 receptor on the basolateral membrane of the collecting duct. The binding of AVP to the V2 receptor, which is coupled to a guanine-nucleotide-binding protein Gs, results in activation of adenylyl cyclase. This results in an increase in intracellular cAMP concentration that mediates the activation of protein kinase A (PKA). Activated PKA p...

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Section: Addison's Disease and Hypopituitarismmentioning

confidence: 99%

Body Water Homeostasis

Schrier¹

2006

Journal of the American Society of Nephrology

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174

110

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“…Los antagonistas de la acción de la vasopresina revierten el trastorno de la retención de agua. La expresión de acuaporina AQP2 aumentada en el tejido medular de dicho animales (14).…”

Section: Discussionunclassified

Severe chronic hiponatremia: rare cause of adrenal insufficiency

Santacruz¹,

Benitez²,

Ayala³

et al. 2016

An. Fac. Cienc. Méd. (Asunción)

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RESUMENLa hiponatremia es el trastorno electrolítico más frecuentemente encontrado en la práctica médica cotidiana y puede llegar a afectar a pacientes tanto en el medio hospitalario como el extrahospitalario.Presentamos el caso de un varón que se presentó a nuestro hospital con una causa de hiponatremia severa, de etiología poco convencional, que respondió satisfactoriamente al tratamiento impartido.Palabras clave: hiponatremia, insuficiencia adrenal, osmolalidad. ABSTRACTHyponatremia is the most common electrolyte disorder encountered in everyday medical practice and can affect patients both in hospital and outside the hospital.We report the case of a man who presented to our hospital with a case of severe hyponatremia, of unconventional etiology, who responded satisfactorily to treatment given

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“…In addition to the baroreceptor-mediated, non-osmotic AVP release secondary to hemodynamic alternations, there is also experimental evidence that glucocorticoid hormone is necessary for maximal suppression of vasopressin synthesis in the hypothalamus (55). In experimental selective glucocorticoid deficiency, the increase in plasma AVP was associated with an upregulation of vasopressin-mediated AQP2 water channels (56). V2 receptor antagonism was associated with reversal of the impaired water excretion and increase in AQP2 expression ( Figure 5) (56).…”

Section: Glucocorticoid Deficiency and Mineralocorticoid Deficiencymentioning

confidence: 99%

Vasopressin and Aquaporin 2 in Clinical Disorders of Water Homeostasis

Schrier

2008

Seminars in Nephrology

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The cloning of the V2 vasopressin receptor was a major advance in understanding the mechanisms involved in regulation of solute-free water excretion by arginine vasopressin (AVP) (1). Subsequently, mutations of the V2 receptor gene were found to account for approximately 85% of cases of congenital nephrogenic diabetes insipidus (2). The mechanisms whereby AVP activates the V2 receptor on the basolateral membrane of the principal cells of the collecting duct and leads to increased water permeability of the apical membrane were, however, quite perplexing. The water transport across the bilipid apical membrane of the principal cells was too fast to be due to diffusion alone. Thus, the shuttle hypothesis was proposed whereby theoretical water channels would be moved from the cytoplasm to the apical membrane of the principal cells by AVP (3). The discovery of the first water channel, aquaporin 1 (AQP1), by Agre and associates led to great excitement in the biomedical community and the awarding of the Nobel Prize in Chemistry in 2003 to Peter Agre (4). Subsequently, aquaporin 2 (AQP2) was identified by Sasaki et al. in the principal cells of the collecting duct (5). Further investigations have demonstrated that AVP is the major regulator of the AQP2 water channels (6). Activation of the V2 receptor on the principal cells of the collecting duct by AVP is associated with a cascade of events involving adenylyl cyclase-mediated cyclic AMP (Figure 1) (7) which leads to both short term and long term regulation of AQP2 (8,9). The short term regulation of AVP involves shuttling the AQP2 containing vesicles from the cytoplasm to the apical membrane. With suppression of vasopressin these apical AQP2 water channels then undergo endocytosis into the cytoplasm (3). The 5' flanking region of the AQP2 gene has a cyclic AMP response element which is involved in the long term upregulation of AQP2 protein expression by AVP (9).The discovery of non-peptide antagonists to the V2 receptor have added yet another important dimension to the understanding of total body water homeostasis (10). These V2 receptor antagonists are agents that specifically block the action of AVP in humans. The several V2 receptor antagonists presently involved in clinical studies are shown in Table 1 (11). In contrast to diuretics, which enhance urine water and electrolyte excretion, the V2 receptor antagonists increase electrolyte-free water excretion.A relative excess of total body water to cation concentration leads to hyponatremia in many clinical circumstances. In fact, hyponatremia is the most frequent electrolyte disturbance in hospitalized patients (12). V2 receptor antagonists have substantial clinical implications, since the majority of the hyponatremic states are due to the non-osmotic release of AVP (13). These V2 receptor antagonists have also been important vehicles to understand several waterPublisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers

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Molecular analysis of impaired urinary diluting capacity in glucocorticoid deficiency

Cited by 31 publications

References 25 publications

Body Water Homeostasis

Body Water Homeostasis

Severe chronic hiponatremia: rare cause of adrenal insufficiency

Vasopressin and Aquaporin 2 in Clinical Disorders of Water Homeostasis

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