Adenylate cyclase responsiveness to hormones in various portions of the human nephron.

Chabardès, Danielle; Gagnan-Brunette, M; Imbert–Teboul, Martine; Gontcharevskaia, O; Montegut, M.; Clique, A.; Morel, François M. M.

doi:10.1172/jci109687

Cited by 154 publications

(74 citation statements)

References 20 publications

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“…However, the effect on the TAL seems to be restricted to rodents (19) and to be part of a series of adaptations of the rodent kidney that improve its urine-concentrating ability (32). Vasopressin does not stimulate adenylate cyclase in the human TAL (which, however, is sensitive to other hormones) (33,34). Thus, it may be assumed that, in this investigation, the change in sodium excretion did not depend on an increase in sodium reabsorption in the TAL.…”

Section: Discussionmentioning

confidence: 63%

Vasopressin-V2 Receptor Stimulation Reduces Sodium Excretion in Healthy Humans

Bankir

Fernandes

Bardoux

et al. 2005

Journal of the American Society of Nephrology

121

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In addition to its effect on water permeability, vasopressin, through its V2 receptors (AVPR2), stimulates Na reabsorption in the collecting duct by increasing the activity of the amiloride-sensitive sodium channel ENaC. This study evaluated whether dDAVP (a potent AVPR2 agonist) reduces sodium excretion in healthy humans (n ‫؍‬ 6) and in patients with central (C; n ‫؍‬ 2) or nephrogenic (N) diabetes insipidus (DI) as a result of mutations of either the aquaporin 2 gene (AQP2; n ‫؍‬ 3) or AVPR2 (n ‫؍‬ 10). dDAVP was infused intravenously (0.3 g/kg body wt in 20 min), and urine was collected for 60 min before (basal) and 150 min after the infusion. dDAVP markedly reduced both urine flow rate and sodium excretion in healthy individuals. A reduction in sodium excretion was also observed in CDI and NDI-AQP2 patients but not in NDI-AVPR2 patients. The magnitude of the fall in sodium excretion correlated with the rise in urine osmolality and the fall in urine output but not with the simultaneously observed fall in mean BP. These results suggest that the dDAVP-induced antinatriuresis is due to a direct V2 receptor-dependent stimulation of sodium reabsorption in the collecting duct and is not secondary to a hemodynamic effect. In conclusion, this study reveals a potent V2-dependent antinatriuretic effect of vasopressin in humans. The possibility that an inappropriate stimulation of ENaC by vasopressin might lead to significant sodium retention in chronic situations remains to be determined. 16: 192016: -192816: , 200516: . doi: 10.1681 I nappropriate retention of sodium and water by the kidney is thought to be a key factor in several forms of hypertension. Thus, it is important to identify factors that may favor excessive sodium reabsorption by the kidney. Vasopressin is known to promote water conservation by increasing the permeability to water of the collecting ducts (CD), thus allowing osmotically driven water reabsorption along these ducts when dilute distal tubular fluid enters them in the cortex and later when they traverse the hyperosmotic medulla. However, the effect of vasopressin on sodium excretion is less clear. A large number of studies have shown that vasopressin infusion increases sodium excretion in vivo in rats, dogs, and sheep (e.g., references 1-4). This natriuretic effect is difficult to reconcile with the fact that, in vitro, vasopressin stimulates sodium reabsorption in the isolated perfused CD (5,6), in the amphibian bladder (a tissue that shares a number of similarities with the mammalian CD) (7), and in several cell lines issued from these two tissues (8 -10). This effect on sodium reabsorption is inhibitable by amiloride and has been shown to result from activation of the endothelial sodium channel ENaC (11). Moreover, chronic elevation of vasopressin or infusion of its V2 agonist dDAVP (12) has been shown to increase the abundance of mRNA (13) and protein (14) of the ␤ and ␥ subunits of ENaC and to enhance markedly the subsequent functional response (water and sodium reabsorption) to exoge...

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Section: Discussionmentioning

confidence: 63%

Vasopressin-V2 Receptor Stimulation Reduces Sodium Excretion in Healthy Humans

Bankir

Fernandes

Bardoux

et al. 2005

Journal of the American Society of Nephrology

121

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“…37,38 CT stimulates adenylyl cyclase activity in human thick ascending limb and in cortical and medullary collecting ducts. 39 In rat, CT-binding sites were detected in the cortical collecting duct and distal convoluted tubule (possibly including the connecting segment) and in thick ascending limbs. 38,40 -42 Quantitative reverse transcription (RT)-PCR detected CT (A) but not CT (B) mRNA in rat kidney, 43 supporting previous work showing that rat kidney has only a single class of CT-binding sites.…”

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confidence: 97%

Calcitonin Has a Vasopressin-like Effect on Aquaporin-2 Trafficking and Urinary Concentration

Bouley¹,

Lu²,

Nunes³

et al. 2011

Journal of the American Society of Nephrology

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The most common cause of hereditary nephrogenic diabetes insipidus is a nonfunctional vasopressin (VP) receptor type 2 (V2R). Calcitonin, another ligand of G-protein-coupled receptors, has a VP-like effect on electrolytes and water reabsorption, suggesting that it may affect AQP2 trafficking. Here, calcitonin increased intracellular cAMP and stimulated the membrane accumulation of AQP2 in LLC-PK1 cells. Pharmacologic inhibition of protein kinase A (PKA) and deficiency of a critical PKA phosphorylation site on AQP2 both prevented calcitonin-induced membrane accumulation of AQP2. Fluorescence assays showed that calcitonin led to a 70% increase in exocytosis and a 20% decrease in endocytosis of AQP2.Immunostaining of rat kidney slices demonstrated that calcitonin induced a significant redistribution of AQP2 to the apical membrane of principal cells in cortical collecting ducts and connecting segments but not in the inner stripe or inner medulla. Calcitonin-treated VP-deficient Brattleboro rats had a reduced urine flow and two-fold higher urine osmolality during the first 12 hours of treatment compared with control groups. Although this VP-like effect of calcitonin diminished over the following 72 hours, the tachyphylaxis was reversible. Taken together, these data show that calcitonin induces cAMP-dependent AQP2 trafficking in cortical collecting and connecting tubules in parallel with an increase in urine concentration. This suggests that calcitonin has a potential therapeutic use in nephrogenic diabetes insipidus.

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“…The distribution of V1a and V2 receptors in the kidney has been well studied in rat and rabbit by radioligand binding studies (18,20,48,57) and several physiological functional assays (17,27,29,31,44). Intrarenal localization of V1a remains less well defined.…”

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confidence: 99%

Axial heterogeneity of vasopressin-receptor subtypes along the human and mouse collecting duct

Carmosino¹,

Brooks²,

Cai³

et al. 2007

American Journal of Physiology-Renal Physiology

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Vasopressin and vasopressin antagonists are finding expanded use in mouse models of disease and in clinical medicine. To provide further insight into the physiological role of V1a and V2 vasopressin receptors in the human and mouse kidney, intrarenal localization of the receptors mRNA was determined by in situ hybridization. V2-receptor mRNA was predominantly expressed in the medulla, whereas mRNA for V1a receptors predominated in the cortex. The segmental localization of vasopressinreceptor mRNAs was determined using simultaneous in situ hybridization and immunohistochemistry for segment-specific markers, including aquaporin-2, Dolichos biflorus agglutinin, epithelial Na channels, Tamm Horsfall glycoprotein, and thiazide-sensitive Na ϩ -Cl Ϫ cotransporter. Notably, V1a receptor expression was exclusively expressed in V-ATPase/anion exchanger-1-labeled alpha-intercalated cells of the medullary collecting duct in both mouse and human kidney. In cortical collecting ducts, V1a mRNA was more widespread and detected in both principal and intercalated cells. V2-receptor mRNA is diffusely expressed along the collecting ducts in both mouse and human kidney, with higher expression levels in the medulla. These results demonstrate heterogenous axial expression of both V1a and V2 vasopressin receptors along the human and mouse collecting duct. The restricted expression of V1a-receptor mRNA in intercalated cells suggests a role for this receptor in acid-base balance. These findings further suggest distinct regulation of renal transport function by AVP through V1a and V2 receptors in the cortex vs. the medulla. in situ hybridization; vasopressin receptors; intercalated cell ARGININE VASOPRESSIN (AVP) is the key hormone responsible for producing a concentrated urine and is secreted in high concentrations during antidiuresis. At least two different vasopressin

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Adenylate cyclase responsiveness to hormones in various portions of the human nephron.

Cited by 154 publications

References 20 publications

Vasopressin-V2 Receptor Stimulation Reduces Sodium Excretion in Healthy Humans

Vasopressin-V2 Receptor Stimulation Reduces Sodium Excretion in Healthy Humans

Calcitonin Has a Vasopressin-like Effect on Aquaporin-2 Trafficking and Urinary Concentration

Axial heterogeneity of vasopressin-receptor subtypes along the human and mouse collecting duct

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