BackgroundIn clinical practice, sodium correction rates are frequently limited in patients with severe hyponatremia to prevent neurologic complications. The implications of on overall mortality and length hospital stay unclear.MethodsIn this multicenter observational study, we evaluated the association mortality, stay, central pontine myelinolysis (CPM) hospitalized (admission serum level less than 120 mEq/l).ResultsThe cohort included 3274 patients. A rate 6 mEq/l/24 hours was observed 38%,...

Nephrogenic diabetes insipidus (NDI) is caused by impairment of vasopressin (VP) receptor type 2 signaling. Because potential therapies for NDI that target the canonical VP/cAMP/protein kinase A pathway have so far proven ineffective, alternative strategies modulating aquaporin (AQP2) trafficking been sought. Successful identification compounds our high–throughput chemical screening assay prompted us to determine whether EGF (EGFR) inhibitors stimulate AQP2 and reduce urine output....

Aquaporin 2 (AQP2) trafficking is regulated by phosphorylation and dephosphorylation of serine residues in the AQP2 COOH terminus. Vasopressin (VP) binding to its receptor (V2R) leads a cascade events that result 256 (S256), S264, S269, but S261. To identify which phosphatase responsible for VP-induced S261 dephosphorylation, we pretreated cells with different inhibitors before VP stimulation. Sanguinarine, specific protein (PP) 2C inhibitor, not PP1, PP2A (okadaic acid), or PP2B...

Key points Aquaporin‐2 (AQP2) is crucial for water homeostasis, and vasopressin (VP) induces AQP2 membrane trafficking by increasing intracellular cAMP, activating PKA causing phosphorylation of at serine 256, 264 269 residues dephosphorylation 261 residue on the C‐terminus. It thought that 256 master regulator trafficking, its has to precede change state other residues. We found Src inhibition causes 256‐independent independently 256. This targeted important inhibition‐induced accumulation;...

We previously showed that in polarized Madin–Darby canine kidney (MDCK) cells, aquaporin-2 (AQP2) is continuously targeted to the basolateral plasma membrane from which it rapidly retrieved by clathrin-mediated endocytosis. It then undertakes microtubule-dependent transcytosis toward apical membrane. In this study, we found treatment with chlorpromazine (CPZ, an inhibitor of endocytosis) results AQP2 accumulation basolateral, but not epithelial cells. MDCK both and clathrin were concentrated...

Aquaporin-2 (AQP2) undergoes constitutive recycling between the cytoplasm and plasma membrane, with an intricate balance endocytosis exocytosis. By inhibiting actin-related protein (Arp)2/3 complex, we prevented AQP2 from entering exocytotic pathway at post- trans-Golgi network level blocked membrane accumulation. Arp2/3 inhibition, therefore, enables us to separate target process, while not affecting endocytosis, thus allowing envisage strategies modulate trafficking treat water disorders.

A 79-year-old man was admitted to this hospital because of hyponatremia and involuntary movements, which would start in the left arm hand then involve side face, such that he look as though grimacing. After received treatment for hyponatremia, movements worsened. diagnosis made.

Vasopressin (VP)-regulated aquaporin-2 (AQP2) trafficking between cytoplasmic vesicles and the plasma membrane of kidney principal cells is essential for water homeostasis. VP affects AQP2 phosphorylation at several serine residues in COOH-terminus; among them, 256 (S256) appears to be a major regulator trafficking. Mutation this aspartic acid, which mimics phosphorylation, induces constitutive expression AQP2. However, intracellular location(s) S256 occurs remains elusive. Here, we used...

Oxidative stress affects a wide variety of cellular processes including morphology, protein traffcking, and cell death. Several studies show that reactive oxygen species (ROS) are able to pass through some water channels, ROS may modulate aquaporin expression traffcking. However, relationship between status the traffcking aquaporin-2 (AQP2) has yet be well-defined. To address this question, we first treated LLC-PK1 cells expressing cmyc-tagged AQP2 (LLC-AQP2 cells) for 30 min with menadione...

In the canonical aquaporin-2 (AQP2) signaling pathway, vasopressin (VP) binds to its V2 receptor, which in turn activates adenylate cyclase and protein kinase A (PKA), resulting AQP2 S256 phosphorylation accumulation of membrane. The epidermal growth factor receptor (EGFR) inhibitor erlotinib also increases membrane accumulation, yet it does not increase cAMP or PKA activity. We hypothesize that ribosomal s6 (RSK), a downstream effector EGFR-MAPK/ERK is terminal phosphorylating this novel...

The cAMP‐sensitive water channel (AQP2) plays an important role in regulation the renal collecting ducts. Upon stimulation by vasopressin (VP), AQP2 is phosphorylated at c‐terminus on serine 256 (pS256). This event leads to accumulation plasma membrane. Other residues including S264 and S269 are also phosphorylated, but phosphorylation of S256 thought be essential membrane accumulation, has precede other residues. Here we show that inhibiting proto‐oncogene tyrosine‐protein kinase Src using...

Impairment of vasopressin (VP) receptor type 2 (V2R) signaling in the kidney is detrimental to water homeostasis. However, strategies targeting cAMP treat diseases associated with balance have so far been unsuccessful humans, prompting a search for alternative pathways that modulate AQP2 trafficking. Our previous study using high-throughput small molecule screening showed AG-490, an EGFR and JAK-2 kinase inhibitor, enhanced membrane expression. Therefore, we tested erlotinib (ERL),...

Aquaporin‐2 (AQP2), the vasopressin (VP)‐sensitive water channel, plays an important role in reabsorption. Accumulation of AQP2 on plasma membrane kidney collecting duct principal cells increases permeability and is necessary for urine concentration. trafficking tightly regulated by phosphorylation dephosphorylation, each four phosphoserine residues (pS256, pS261, pS264 pS269) has been intensively studied. Recent work our laboratory shown that erlotinib (Erl), epidermal growth factor...

Intercalated cells (IC) in kidney collecting ducts are essential for acid‐base homeostasis. A proteomic analysis of these after purification by FACS revealed unexpectedly that they express high levels neprilysin, a neutral protease, previously reported to be located the brush border proximal tubule cells. Therefore, we re‐examined distribution neprilysin immunohistochemistry and western blot analysis. Using anti‐neprilysin antibodies two duct markers: anti‐AQP2 antibody (principal cells)...

Aquaporin 2 (AQP2) is a water channel protein located primarily on principal cells of kidney collecting ducts, and crucial for regulating body homeostasis. Regulation AQP2 trafficking subject to hormonal control, mainly via the canonical vasopressin (VP) signaling pathway which stimulates membrane accumulation. Active actin cytoskeleton remodeling also plays an important role in trafficking, but mechanism incompletely understood. Using immunohistochemistry confocal microscopy, we discovered...

Abstract Vasopressin (VP) activates PKA, resulting in phosphorylation and membrane accumulation of aquaporin-2 (AQP2). Epidermal growth factor receptor (EGFR) inhibition with erlotinib also induces AQP2 trafficking a pattern similar to VP, but without increasing PKA activity. Here, we identify the ribosomal s6 kinase (RSK) as final mediator phosphorylating this novel, erlotinib-induced pathway. We found that RSK was expressed medullary principal cells rat kidneys. BI-D1870 or siRNA blocked...