Liver X receptor agonists decrease ENaC-mediated sodium transport in collecting duct cells

2012 ◽  
Vol 303 (12) ◽  
pp. F1610-F1616 ◽  
Author(s):  
Sunhapas Soodvilai ◽  
Zhanjun Jia ◽  
Somsak Fongsupa ◽  
Varanuj Chatsudthipong ◽  
Tianxin Yang
Keyword(s):  
Sodium Transport ◽  
Collecting Duct ◽  
Primary Cultures ◽  
Membrane Expression ◽  
Natural Ligand ◽  
Duct Cells ◽  
Renal Action ◽  
Collecting Duct Cells ◽  
X Receptors ◽  
Lxr Agonists

Liver X receptors (LXRs) are nuclear receptors that regulate cholesterol, fatty acid, and glucose metabolism in various tissues. However, the renal action of LXRs is not well understood. Here we investigated the effects of LXR-activating ligands on modulation of epithelial sodium channel (ENaC)-mediated sodium transport in collecting duct cells. Exposure of the M1 cells to the synthetic LXR agonists T0901317 and GW3965 or the natural ligand 22R-hydroxycholesterol for 24 h decreased amiloride-sensitive sodium transport, corresponding with an increase of transepithelial resistance. The inhibition of amiloride-sensitive sodium transport after incubation with T0901317 or GW3965 was not mediated by a reduction of Na+/K+-ATPase-mediated basolateral sodium transport. On the other hand, T0901317 and GW3965 decreased mRNA abundance and membrane expression of ENaC. Preincubation the monolayer with GW3965 attenuated aldosterone-induced stimulation sodium transport. In primary cultures of collecting duct cells, T0901317 and GW3965 similarly inhibited ENaC transport function as in M1 cells. This is the first evidence showing LXR-activating ligands modulate ENaC-mediated sodium transport in collecting duct cells. These results suggest that LXRs may represent a novel therapeutic target for treatment of conditions with dysregulation of ENaC such as hypertension.

117 PAR-2 RECEPTORS STIMULATE SODIUM TRANSPORT IN COLLECTING DUCT CELLS.

2004 ◽  
Vol 52 (Suppl 1) ◽  
pp. S277.4-S277
Author(s):  
K S Hering-Smith ◽  
M C Carmichael ◽  
F R Schiro ◽  
L L Hamm
Keyword(s):  
Sodium Transport ◽  
Collecting Duct ◽  
Duct Cells ◽  
Collecting Duct Cells

scholarly journals Soluble (pro)renin receptor via β-catenin enhances urine concentration capability as a target of liver X receptor

2016 ◽  
Vol 113 (13) ◽  
pp. E1898-E1906 ◽  
Author(s):  
Xiaohan Lu ◽  
Fei Wang ◽  
Chuanming Xu ◽  
Sunny Soodvilai ◽  
Kexin Peng ◽  
...  
Keyword(s):  
Diabetes Insipidus ◽  
Biological Fluid ◽  
Collecting Duct ◽  
Urine Concentration ◽  
Potential Interaction ◽  
Protein Protein Interaction ◽  
Duct Cells ◽  
Collecting Duct Cells ◽  
X Receptors ◽  
Antidiuretic Action

The extracellular domain of the (pro)renin receptor (PRR) is cleaved to produce a soluble (pro)renin receptor (sPRR) that is detected in biological fluid and elevated under certain pathological conditions. The present study was performed to define the antidiuretic action of sPRR and its potential interaction with liver X receptors (LXRs), which are known regulators of urine-concentrating capability. Water deprivation consistently elevated urinary sPRR excretion in mice and humans. A template-based algorithm for protein–protein interaction predicted the interaction between sPRR and frizzled-8 (FZD8), which subsequently was confirmed by coimmunoprecipitation. A recombinant histidine-tagged sPRR (sPRR-His) in the nanomolar range induced a remarkable increase in the abundance of renal aquaporin 2 (AQP2) protein in primary rat inner medullary collecting duct cells. The AQP2 up-regulation relied on sequential activation of FZD8-dependent β-catenin signaling and cAMP–PKA pathways. Inhibition of FZD8 or tankyrase in rats induced polyuria, polydipsia, and hyperosmotic urine. Administration of sPRR-His alleviated the symptoms of diabetes insipidus induced in mice by vasopressin 2 receptor antagonism. Administration of the LXR agonist TO901317 to C57/BL6 mice induced polyuria and suppressed renal AQP2 expression associated with reduced renal PRR expression and urinary sPRR excretion. Administration of sPRR-His reversed most of the effects of TO901317. In cultured collecting duct cells, TO901317 suppressed PRR protein expression, sPRR release, and PRR transcriptional activity. Overall we demonstrate, for the first time to our knowledge, that sPRR exerts antidiuretic action via FZD8-dependent stimulation of AQP2 expression and that inhibition of this pathway contributes to the pathogenesis of diabetes insipidus induced by LXR agonism.

PAR-2 RECEPTORS STIMULATE SODIUM TRANSPORT IN COLLECTING DUCT CELLS.

2004 ◽  
Vol 52 ◽  
pp. S277
Author(s):  
K S Hering-Smith ◽  
M C Carmichael ◽  
F R Schiro ◽  
L L Hamm
Keyword(s):  
Sodium Transport ◽  
Collecting Duct ◽  
Duct Cells ◽  
Collecting Duct Cells

A hyperpolarization-activated, cyclic nucleotide-gated, (Ih-like) cationic current and HCN gene expression in renal inner medullary collecting duct cells

2008 ◽  
Vol 294 (4) ◽  
pp. C893-C906 ◽  
Author(s):  
Juan J. Bolívar ◽  
Dagoberto Tapia ◽  
Gabina Arenas ◽  
Mauricio Castañón-Arreola ◽  
Haydee Torres ◽  
...  
Keyword(s):  
Cyclic Nucleotide ◽  
Mammalian Cells ◽  
Cultured Cells ◽  
Collecting Duct ◽  
Primary Cultures ◽  
Inner Medullary Collecting Duct ◽  
Cationic Current ◽  
Duct Cells ◽  
Collecting Duct Cells ◽  
Medullary Collecting Duct

The cation conductancein primary cultures of rat renal inner medullary collecting duct was studied using perforated-patch and conventional whole cell clamp techniques. Hyperpolarizations beyond −60 mV induced a time-dependent inward nonselective cationic current ( Ivti) that resembles the well-known hyperpolarization-activated, cyclic nucleotide-gated Ih and If currents. Ivti showed a half-maximal activation around −102 mV with a slope factor of 25 mV. It had a higher conductance (but, at its reversal potential, not a higher permeability) for K+ than for Na+ ( gK+/ gNa+ = 1.5), was modulated by cAMP and blocked by external Cd2+ (but not Cs+ or ZD-7288), and potentiated by a high extracellular K+ concentration. We explored the expression of the Ih channel genes (HCN1 to -4) by RT-PCR. The presence of transcripts corresponding to the HCN1, -2, and -4 genes was observed in both the cultured cells and kidney inner medulla. Western blot analysis with HCN2 antibody showed labeling of ∼90- and ∼120-kDa proteins in samples from inner medulla and cultured cells. Immunocytochemical analysis of cell cultures and inner medulla showed the presence of HCN immunoreactivity partially colocalized with the Na+-K+-ATPase at the basolateral membrane of collecting duct cells. This is the first evidence of an Ih-like cationic current and HCN immunoreactivity in either kidney or any other nonexcitable mammalian cells.

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