Effects of chronic hypercapnia on ammonium transport in the mouse kidney.

Hypercapnia and subsequent respiratory acidosis are serious complications in many patients with respiratory disorders. The acute response to hypercapnia is buffering of H by hemoglobin and cellular proteins but this effect is limited. The chronic response is renal compensation that increases HCO reabsorption, and stimulates urinary excretion of titratable acids (TA) and NH .

Calcium receptor signaling and citrate transport.

The calcium sensing receptor (CaSR) in the distal nephron decreases the propensity for calcium stones. Here we investigate if the apical CaSR in the proximal tubule also prevents stone formation acting via regulation of apical dicarboxylate and citrate transport. Urinary citrate, partially reabsorbed as a dicarboxylate in the proximal tubule lumen, inhibits stone formation by complexing calcium.

p63+ ureteric bud tip cells are progenitors of intercalated cells.

During renal branching morphogenesis, ureteric bud tip cells (UBTC) serve as the progenitor epithelium for all cell types of the collecting duct. While the transcriptional circuitry of ureteric bud (UB) branching has been intensively studied, the transcriptional control of UBTC differentiation has been difficult to ascertain. This is partly due to limited knowledge of UBTC-specific transcription factors that mark the progenitor state.

Effect of NBCe1 deletion on renal citrate and 2-oxoglutarate handling.

Unlabelled: The bicarbonate transporter, NBCe1 (SLC4A4), is necessary for at least two components of the proximal tubule contribution to acid-base homeostasis, filtered bicarbonate reabsorption, and ammonia metabolism. This study's purpose was to determine NBCe1's role in a third component of acid-base homeostasis, organic anion metabolism, by studying mice with NBCe1 deletion. Because NBCe1 deletion causes metabolic acidosis, we also examined acid-loaded wild-type adult mice to determine if the effects of NBCe1 deletion were specific to NBCe1 deletion or were a non-specific effect of the associated metabolic acidosis.

Acid-Base Homeostasis.

Acid-base homeostasis and pH regulation are critical for both normal physiology and cell metabolism and function. The importance of this regulation is evidenced by a variety of physiologic derangements that occur when plasma pH is either high or low. The kidneys have the predominant role in regulating the systemic bicarbonate concentration and hence, the metabolic component of acid-base balance.

The Cap1-claudin-4 regulatory pathway is important for renal chloride reabsorption and blood pressure regulation.

The paracellular pathway through the tight junction provides an important route for transepithelial chloride reabsorption in the kidney, which regulates extracellular salt content and blood pressure. Defects in paracellular chloride reabsorption may in theory cause deregulation of blood pressure. However, there is no evidence to prove this theory or to demonstrate the in vivo role of the paracellular pathway in renal chloride handling.

Localization of the calcium-regulated citrate transport process in proximal tubule cells.

Urinary citrate is an important inhibitor of calcium-stone formation. Most of the citrate reabsorption in the proximal tubule is thought to occur via a dicarboxylate transporter NaDC1 located in the apical membrane. OK cells, an established opossum kidney proximal tubule cell line, transport citrate but the characteristics change with extracellular calcium such that low calcium solutions stimulate total citrate transport as well as increase the apparent affinity for transport.

Acid-base and potassium homeostasis.

Acid-base balance and potassium disorders are often clinically linked. Importantly, acid-base disorders alter potassium transport. In general, acidosis causes decreased K(+) secretion and increased reabsorption in the collecting duct.

Pivotal role of the kidney in hypertension.

The kidneys play a pivotal role in causing some forms of hypertension and probably a permissive role in most, if not all, forms of hypertension. This concept of the critical role of the kidneys has been postulated for many years but has been solidified by the molecular unraveling of several monogenic forms of hypertension such as Liddle's syndrome, apparent mineralocorticoid excess and glucocorticoid-remedial aldosteronism. These and other hypertensive disorders cause sodium retention through excess Na reabsorption in the distal nephron.

Interleukin-6 stimulates epithelial sodium channels in mouse cortical collecting duct cells.

The aim of this study is to elucidate the effects of interleukin-6 (IL-6) on the expression and activity of the epithelial sodium channel (ENaC), which is one of the key mechanisms underlying tubular sodium reabsorption. M-1 cortical collecting duct cells were treated with IL-6 (100 ng/ml) for 12 h. Real-time polymerase chain reaction and immunoblotting were employed to examine the mRNA and protein abundance.

Regulation of sodium transport by ENaC in the kidney.

Purpose Of Review: The amiloride-sensitive epithelial sodium channel (ENaC) plays a major role in the regulation of sodium transport in the collecting duct and hence sodium balance. This review describes recent findings in the regulation of ENaC function by serine proteases in particular and other regulatory aspects.

Recent Findings: Regulation of ENaC occurs at many levels (biophysical, transcriptional, post-translational modifications, assembly, membrane insertion, retrieval, recycling, degradation, etc.

Myeloma light chains induce epithelial-mesenchymal transition in human renal proximal tubule epithelial cells.

Background: To determine the role of epithelial-mesenchymal transition (EMT) as a potential mechanism contributing to the characteristic tubulointerstitial renal fibrosis in multiple myeloma, we examined whether myeloma light chains (LCs) directly induce EMT in human renal proximal tubule epithelial cells (PTECs).

Methods: As positive controls we used TGF-beta1 and cyclosporine A (CsA), two agents known to induce EMT in PTECs. Human LCs were isolated and purified from the urine of myeloma patients with modest renal insufficiency without evidence of glomerular involvement.

Expression of the rat renal PiT-2 phosphate transporter.

Background: NaPi-2a is the main sodium-dependent Pi (Na+-Pi) transporter in the apical membrane of the renal proximal tubule. Another group of Pi transporters, Glvr-1 (PiT-1) and Ram-1 (PiT-2), was identified. The PiT-2 cRNA induces Na+-dependent Pi uptake into Xenopus laevis oocytes.

Characteristics of renal Rhbg as an NH4(+) transporter.

Rhbg is one of two recently cloned nonerythroid glycoproteins belonging to the Rh antigen family. Rhbg is expressed in basolateral membranes of intercalated cells of the kidney cortical collecting duct and some other cell types of the distal nephron and may function as NH(4)(+) transporters. The aim of this study was to characterize the role of Rhbg in transporting NH(4)(+).

Enhancement of collecting duct renin in angiotensin II-dependent hypertensive rats.

Distal nephron renin may provide a possible pathway for angiotensin (Ang) I generation from proximally delivered angiotensinogen. To examine the effects of Ang II on distal nephron renin, we compared renin protein and mRNA expression in control and Ang II-infused rats. Kidneys from sham (n=9) and Ang II-infused (80 ng/kg per minute, 13 days, n=10) Sprague-Dawley rats were processed by immunohistochemistry, Western blot, reverse transcriptase-polymerase chain reaction (RT-PCR), and quantitative real-time RT-PCR.

Pathophysiology of hypocitraturic nephrolithiasis.

Urinary citrate inhibits calcium stone formation by complexing calcium in a soluble form and by effects on urinary crystals to prevent growth to stones. Low urinary citrate has been recognized for several decades as a contributing factor in some stone forming patients, but recent studies have elucidated the mechanisms and derangements of the renal handling of citrate in various conditions. In addition, oral citrate as an alkalinizing agent can not only increase urinary citrate, but also favorably impact other stone-promoting conditions.

Serine protease activity in m-1 cortical collecting duct cells.

An apical serine protease, channel-activating protease 1 (CAP1), augments sodium transport in A6 cells. Prostasin, a novel serine protease originally purified from seminal fluid, has been proposed to be the mammalian ortholog of CAP1. We have recently found functional evidence for a similar protease activity in the M-1 cortical collecting duct cell line.

Ammonium interaction with the epithelial sodium channel.

The purpose of this study was to investigate the direct effect of NH(3)/NH on mouse epithelial Na(+) channels (mENaC) expressed in Xenopus oocytes. Two-electrode voltage-clamp and ion-selective microelectrodes were used to measure the Na(+) current, intracellular pH (pH(i)), and ion activities in oocytes expressing mENaC. In oocytes expressing mENaC, removal of external Na(+) reversibly hyperpolarized membrane potential by 129 +/- 5.

Transport of NH(3)/NH in oocytes expressing aquaporin-1.

The aim of this study was to determine whether expressing aquaporin (AQP)-1 could affect transport of NH(3). Using ion-selective microelectrodes, the experiments were conducted on frog oocytes (cells characterized by low NH(3) permeability) expressing AQP1. In H(2)O-injected oocytes, exposure to NH(3)/NH (20 mM, pH 7.

Citrate and succinate transport in proximal tubule cells.

Urinary citrate, which inhibits calcium nephrolithiasis, is determined by proximal reabsorption via an apical dicarboxylate transporter. Citrate is predominantly trivalent at physiological pH, but citrate(-2) is transported at the apical membrane. We now demonstrate that low-Ca solutions induce transport of citrate(-2) and succinate in opossum kidney cells.

Regulation of sodium transport in M-1 cells.

The M-1 cell line, derived from the mouse cortical collecting duct (CCD), is being used as a mammalian model of the CCD to study Na+ transport. The present studies aimed to further define the role of various hormones in affecting Na+ transport in M-1 cells grown in defined media. M-1 cells on permeable support, in serum-free media, developed amiloride-sensitive current 4-5 days after seeding.

Metabolic support of collecting duct transport.

The present studies address the metabolic processes that support the reabsorption of sodium and the secretion of bicarbonate in the interspersed but distinct principal and intercalated cells of the cortical collecting duct (CCD). In microperfused rabbit CCD, sodium reabsorption was measured by lumen-to-bath 22Na flux, and bicarbonate transport was assayed by microcalorimetry. Flux measurements were made before and after metabolic substrate changes or application of metabolic inhibitors.