scholarly journals Role of collecting duct principal cell NOS1β in sodium and potassium homeostasis

2021 ◽  
Vol 9 (20) ◽  
Author(s):  
Kelly A. Hyndman ◽  
Elena Isaeva ◽  
Oleg Palygin ◽  
Luciano D. Mendoza ◽  
Aylin R. Rodan ◽  
...  
Keyword(s):  
Collecting Duct ◽  
Principal Cell ◽  
Potassium Homeostasis ◽  
Sodium And Potassium

Sodium and potassium handling by the aldosterone-sensitive distal nephron: the pivotal role of the distal and connecting tubule

2004 ◽  
Vol 287 (4) ◽  
pp. F593-F601 ◽  
Author(s):  
Pierre Meneton ◽  
Johannes Loffing ◽  
David G. Warnock
Keyword(s):  
Sodium Intake ◽  
Collecting Duct ◽  
Genetic Defect ◽  
Potassium Transport ◽  
The Body ◽  
Dietary Sodium ◽  
Sodium Reabsorption ◽  
Connecting Tubule ◽  
Sodium And Potassium

Sodium reabsorption and potassium secretion in the distal convoluted tubule and in the connecting tubule can maintain the homeostasis of the body, especially when dietary sodium intake is high and potassium intake is low. Under these conditions, a large proportion of the aldosterone-regulated sodium and potassium transport would occur in these nephron segments before the tubular fluid reaches the collecting duct. The differences between these two segments and the collecting duct would be more quantitative than qualitative. The collecting duct would come into play when the upstream segments are overloaded by a primary genetic defect that affects sodium and/or potassium transport or by a diet that is exceedingly poor in sodium and rich in potassium. It is likely that the homeostatic role of the distal convoluted and connecting tubules, which are technically difficult to study, has been underestimated, whereas the role of the more easily accessible collecting duct may have been overemphasized.

The Renal Outer Medullary Potassium Channel (ROMK): An Intriguing Pharmacological Target for an Innovative Class of Diuretic Drugs

2018 ◽  
Vol 25 (23) ◽  
pp. 2627-2636 ◽  
Author(s):  
Vincenzo Calderone ◽  
Alma Martelli ◽  
Eugenia Piragine ◽  
Valentina Citi ◽  
Lara Testai ◽  
...  
Keyword(s):  
Physiological Role ◽  
Clinical Use ◽  
Diuretic Activity ◽  
First Line ◽  
Potassium Homeostasis ◽  
Diuretic Drugs ◽  
Pharmacological Target ◽  
Diuretic Agents ◽  
Effective Drugs

In the last four decades, the several classes of diuretics, currently available for clinical use, have been the first line option for the therapy of widespread cardiovascular and non-cardiovascular diseases. Diuretic drugs generally exhibit an overall favourable risk/benefit balance. However, they are not devoid of side effects. In particular, all the classes of diuretics cause alteration of potassium homeostasis. <p> In recent years, understanding of the physiological role of the renal outer medullary potassium (ROMK) channels, has shown an intriguing pharmacological target for developing an innovative class of diuretic agents: the ROMK inhibitors. This novel class is expected to promote diuretic activity comparable to (or even higher than) that provided by the most effective drugs used in clinics (such as furosemide), with limited effects on potassium homeostasis. <p> In this review, the physio-pharmacological roles of ROMK channels in the renal function are reported, along with the most representative molecules which have been currently developed as ROMK inhibitors.

scholarly journals With-No-Lysine Kinase 1 (WNK1) Augments TRPV4 Function in the Aldosterone-Sensitive Distal Nephron

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1482
Author(s):  
Viktor N. Tomilin ◽  
Kyrylo Pyrshev ◽  
Naghmeh Hassanzadeh Khayyat ◽  
Oleg Zaika ◽  
Oleh Pochynyuk
Keyword(s):  
Collecting Duct ◽  
Chinese Hamster ◽  
Dominant Negative ◽  
K Channel ◽  
Apical Plasma Membrane ◽  
Dependent Manner ◽  
Distal Nephron ◽  
Potassium Homeostasis ◽  
Wnk Kinases ◽  
K Secretion

Kidneys play a central role in regulation of potassium homeostasis and maintenance of plasma K+ levels within a narrow physiological range. With-no-lysine (WNK) kinases, specifically WNK1 and WNK4, have been recognized to regulate K+ balance, in part, by orchestrating maxi K+ channel (BK)-dependent K+ secretion in the aldosterone-sensitive distal nephron (ASDN), which includes the connecting tubule and collecting duct. We recently demonstrated that the Ca2+-permeable TRPV4 channel is essential for BK activation in the ASDN. Furthermore, high K+ diet increases TRPV4 activity and expression largely in an aldosterone-dependent manner. In the current study, we aimed to test whether WNK kinases contribute to regulation of TRPV4 activity and its stimulation by aldosterone. Systemic inhibition of WNK with WNK463 (1 mg/kgBW for 3 days) markedly decreased TRPV4-dependent Ca2+ influx in freshly isolated split-opened collecting ducts. Aldosterone greatly increased TRPV4 activity and expression in cultured mpkCCDc14 cells and this effect was abolished in the presence of WNK463. Selective inhibition of WNK1 with WNK-in-11 (400 nM, 24 h) recapitulated the effects of WNK463 on TRPV4-dependent Ca2+ influx. Interestingly, WNK-in-11 did not interfere with up-regulation of TRPV4 expression by aldosterone, but prevented translocation of the channel to the apical plasma membrane. Furthermore, co-expression of TRPV4 and WNK1 into Chinese hamster ovary (CHO) cells increased the macroscopic TRPV4-dependent cation currents. In contrast, over-expression of TRPV4 with a dominant negative WNK1 variant (K233M) decreased the whole-cell currents, suggesting both stimulatory and permissive roles of WNK1 in regulation of TRPV4 activity. Overall, we show that WNK1 is essential for setting functional TRPV4 expression in the ASDN at the baseline and in response to aldosterone. We propose that this new mechanism contributes to regulation of K+ secretion and, by extension, urinary K+ levels to maintain systemic potassium homeostasis.

scholarly journals Role of hepcidin in oxidative stress and cell death of cultured mouse renal collecting duct cells: protection against iron and sensitization to cadmium

2021 ◽  
Author(s):  
Stephanie Probst ◽  
Johannes Fels ◽  
Bettina Scharner ◽  
Natascha A. Wolff ◽  
Eleni Roussa ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Cell Fate ◽  
Catalase Activity ◽  
Metal Ion ◽  
Iron Homeostasis ◽  
Collecting Duct ◽  
Duct Cell ◽  
Plasmid Transfection

AbstractThe liver hormone hepcidin regulates systemic iron homeostasis. Hepcidin is also expressed by the kidney, but exclusively in distal nephron segments. Several studies suggest hepcidin protects against kidney damage involving Fe2+ overload. The nephrotoxic non-essential metal ion Cd2+ can displace Fe2+ from cellular biomolecules, causing oxidative stress and cell death. The role of hepcidin in Fe2+ and Cd2+ toxicity was assessed in mouse renal cortical [mCCD(cl.1)] and inner medullary [mIMCD3] collecting duct cell lines. Cells were exposed to equipotent Cd2+ (0.5–5 μmol/l) and/or Fe2+ (50–100 μmol/l) for 4–24 h. Hepcidin (Hamp1) was transiently silenced by RNAi or overexpressed by plasmid transfection. Hepcidin or catalase expression were evaluated by RT-PCR, qPCR, immunoblotting or immunofluorescence microscopy, and cell fate by MTT, apoptosis and necrosis assays. Reactive oxygen species (ROS) were detected using CellROX™ Green and catalase activity by fluorometry. Hepcidin upregulation protected against Fe2+-induced mIMCD3 cell death by increasing catalase activity and reducing ROS, but exacerbated Cd2+-induced catalase dysfunction, increasing ROS and cell death. Opposite effects were observed with Hamp1 siRNA. Similar to Hamp1 silencing, increased intracellular Fe2+ prevented Cd2+ damage, ROS formation and catalase disruption whereas chelation of intracellular Fe2+ with desferrioxamine augmented Cd2+ damage, corresponding to hepcidin upregulation. Comparable effects were observed in mCCD(cl.1) cells, indicating equivalent functions of renal hepcidin in different collecting duct segments. In conclusion, hepcidin likely binds Fe2+, but not Cd2+. Because Fe2+ and Cd2+ compete for functional binding sites in proteins, hepcidin affects their free metal ion pools and differentially impacts downstream processes and cell fate.

scholarly journals Role of Collecting Duct AT1a Receptors in Concentrating Urine

2011 ◽  
Vol 22 (12) ◽  
pp. 2144-2145
Author(s):  
Oleh Pochynyuk ◽  
James D. Stockand
Keyword(s):  
Collecting Duct

scholarly journals Role of the medullary collecting duct in potassium excretion in potassium-adapted animals

1981 ◽  
Vol 20 (5) ◽  
pp. 655-662 ◽  
Author(s):  
Donald A. Schon ◽  
Karen A. Backman ◽  
John P. Hayslett
Keyword(s):  
Collecting Duct ◽  
Potassium Excretion ◽  
Medullary Collecting Duct

Abstract 103: Soluble (Pro)Renin Receptor Targets Renal V2 Vasopressin Receptor to Enhance Urine Concentrating Capability

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Fei Wang ◽  
Nirupama Ramkumar ◽  
Kexin Peng ◽  
Xiaohan Lu ◽  
Long Zhao ◽  
...  
Keyword(s):  
Biological Fluid ◽  
Collecting Duct ◽  
Urine Volume ◽  
Neutralizing Antibody ◽  
Fold Increase ◽  
Medium Level ◽  
V2 Vasopressin Receptor ◽  
Receptor Targets ◽  
Renal Expression

The extracellular domain of (pro)renin receptor (PRR) is cleaved to produce a 28 kDa soluble receptor (sPRR) which is detected in biological fluid and elevated under certain pathological conditions. Our recent work suggests that sPRR derived from collecting duct intercalated cells acts in a paracrine fashion to regulate water transport in the principal cells. The present study attempted to further define the role of sPRR in vasopressin (AVP) signaling with emphasis on V2R regulation. In primary rat IMCD cells, treatment with a recombinant sPRR termed as sPRR-His at 10 nM for 12 h induced a 2.8 -fold increase in V2R protein and a 2-fold increase in V2R mRNA. Following AVP treatment, V2R protein expression was increased by 3-fold, which was blunted by a PRR antagonist (PRO20) and a PRR neutralizing antibody. Mice with CD-specific (CD PRR KO) developed a medium level of diabetes insipidus (urine volume: KO: 2.2±0.4 versus Floxed: 1.2±0.3 ml/day; P <0.05), accompanied with a 60% reduction of renal V2R protein and a 25% reduction of urinary sPRR excretion. Adminstration of sPRR-His at for 3 d almost completely rescued the polyuria phenotype of CD PRR KO mice (urine volume: KO+sPRR-His: 1.6±0.3 vs. KO: 2.4±0.5 ml/day, p <0.05) associated with restoration of renal V2R protein and AQP2 protein abundances. Interestingly, nephron-specific PRR KO (Neph PRR KO) exhibited more robust polyuria (urine volume: KO: 7.3±1.1 vs. Floxed: 1.2±0.5 ml/day, p <0.01) associated with suppressed renal expression of AQP2, NKCC2, and V2R. Administration of sPRR-His to Neph PRR KO mice partially attenuated polyuria (urine volume: KO+sPRR-His: 4.1±1.2 vs. KO: 7.3±1.1 ml/day, p <0.01) accompanied by restored renal expression of V2R and AQP2, as well as AVP sensitivity. In contrast, the downregulation of NKCC2 expression in the null mice was unaffected by sPRR-His infusion nor was the upregulation of autophagosome marker microtubule-associated protein 1A/1B-light chain 3 (LC3b). Together, our data suggests that sPRR selectively targets the CD to determine V2R expression and hence AVP sensitivity and urine concentrating capability, independently of autophagosome accumulation.

Polaris, a protein disrupted inorpkmutant mice, is required for assembly of renal cilium

2002 ◽  
Vol 282 (3) ◽  
pp. F541-F552 ◽  
Author(s):  
Bradley K. Yoder ◽  
Albert Tousson ◽  
Leigh Millican ◽  
John H. Wu ◽  
Charles E. Bugg ◽  
...  
Keyword(s):  
Primary Cilia ◽  
Collecting Duct ◽  
Physiological Role ◽  
Duct Cell ◽  
Cystic Kidney Disease ◽  
Cystic Kidney ◽  
Apical Surface ◽  
Cystic Disease ◽  
Cortical Collecting Duct

Cilia are organelles that play diverse roles, from fluid movement to sensory reception. Polaris, a protein associated with cystic kidney disease in Tg737°rpkmice, functions in a ciliogenic pathway. Here, we explore the role of polaris in primary cilia on Madin-Darby canine kidney cells. The results indicate that polaris localization and solubility change dramatically during cilia formation. These changes correlate with the formation of basal bodies and large protein rafts at the apical surface of the epithelia. A cortical collecting duct cell line has been derived from mice with a mutation in the Tg737 gene. These cells do not develop normal cilia, which can be corrected by reexpression of the wild-type Tg737 gene. These data suggest that the primary cilia are important for normal renal function and/or development and that the ciliary defect may be a contributing factor to the cystic disease in Tg737°rpkmice. Further characterization of these cells will be important in elucidating the physiological role of renal cilia and in determining their relationship to cystic disease.

Sign in / Sign up

Export Citation Format

Share Document