Alterations in gene expression and microbiome composition upon calcium-sensing receptor deletion in the mouse esophagus.

The calcium-sensing receptor (CaSR), a G protein-coupled receptor, regulates Ca concentration in plasma by regulating parathyroid hormone secretion. In other tissues, it is reported to play roles in cellular differentiation and migration and in secretion and absorption. We reported previously that CaSR can be conditionally deleted in the mouse esophagus.

Proton-pump inhibitor vs. H2-receptor blocker use and overall risk of CKD progression.

Background: The relationship between proton-pump inhibitor (PPI) use and chronic kidney disease (CKD) progression remains controversial. Specifically, there is a lack of data evaluating renal outcomes in established CKD patients. The aim of our study is to determine the risk of progression to end-stage kidney disease (ESKD) or death amongst CKD patients on PPI, histamine-2 receptor blocker (H2B), or no anti-acid therapy.

The Effect of Proton Pump Inhibitor Use on the Course of Kidney Function in Patients with Chronic Kidney Disease Stages G3a to G4.

Background: Proton pump inhibitors (PPI) are widely used and implicated in the progression of chronic kidney disease (CKD). We evaluated the relation between chronic PPI use in veterans with CKD G3a to G4 and the rate of decline in renal function.

Methods: We accessed the Veteran Affairs Informatics and Computing Infrastructure national database to evaluate the relation between chronic PPI use and rate of decline in renal function in veterans with CKD (eGFR <60 ml/min1.

Ussing Chamber Methods to Study the Esophageal Epithelial Barrier.

The Ussing chamber was developed in 1949 by Hans Ussing and quickly became a powerful tool to study ion and solute transport in epithelia. The chamber has two compartments strictly separating the apical and basolateral sides of the tissue under study. The two sides of the tissue are connected via electrodes to a modified electrometer/pulse generator that allows measurement of electrical parameters, namely, transepithelial voltage, current, and resistance.

Calcium-sensing receptor deletion in the mouse esophagus alters barrier function.

Calcium-sensing receptor (CaSR) is the molecular sensor by which cells respond to small changes in extracellular Ca concentrations. CaSR has been reported to play a role in glandular and fluid secretion in the gastrointestinal tract and to regulate differentiation and proliferation of skin keratinocytes. CaSR is present in the esophageal epithelium, but its role in this tissue has not been defined.

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 .

Structural determinants of NH3 and NH4+ transport by mouse Rhbg, a renal Rh glycoprotein.

Renal Rhbg is localized to the basolateral membrane of intercalated cells and is involved in NH/NH transport. The structure of Rhbg is not yet resolved; however, a high-resolution crystal structure of AmtB, a bacterial homolog of Rh, has been determined. We aligned the sequence of Rhbg to that of AmtB and identified important sites of Rhbg that may affect transport.

Cytoskeletal changes induced by allosteric modulators of calcium-sensing receptor in esophageal epithelial cells.

The calcium-sensing receptor (CaSR), a G-protein-coupled receptor, plays a role in glandular and fluid secretion in the gastrointestinal tract, and regulates differentiation and proliferation of epithelial cells. We examined the expression of CaSR in normal and pathological conditions of human esophagus and investigated the effect of a CaSR agonist, cinacalcet (CCT), and antagonist, calhex (CHX), on cell growth and cell-cell junctional proteins in primary cultures of porcine stratified squamous esophageal epithelium. We used immunohistochemistry and Western analysis to monitor expression of CaSR and cell-cell adhesion molecules, and MTT assay to monitor cell proliferation in cultured esophageal cells.

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.

Mechanisms of ammonia and ammonium transport by rhesus-associated glycoproteins.

In this study we characterized ammonia and ammonium (NH3/NH4(+)) transport by the rhesus-associated (Rh) glycoproteins RhAG, Rhbg, and Rhcg expressed in Xenopus oocytes. We used ion-selective microelectrodes and two-electrode voltage clamp to measure changes in intracellular pH, surface pH, and whole cell currents induced by NH3/NH4(+) and methyl amine/ammonium (MA/MA(+)). These measurements allowed us to define signal-specific signatures to distinguish NH3 from NH4(+) transport and to determine how transport of NH3 and NH4(+) differs among RhAG, Rhbg, and Rhcg.

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.

Alterations in junctional proteins, inflammatory mediators and extracellular matrix molecules in eosinophilic esophagitis.

Eosinophilic esophagitis (EoE), an inflammatory atopic disease of the esophagus, causes massive eosinophil infiltration, basal cell hyperplasia, and sub-epithelial fibrosis. To elucidate cellular and molecular factors involved in esophageal tissue damage and remodeling, we examined pinch biopsies from EoE and normal pediatric patients. An inflammation gene array confirmed that eotaxin-3, its receptor CCR3 and interleukins IL-13 and IL-5 were upregulated.

Characteristics of mammalian Rh glycoproteins (SLC42 transporters) and their role in acid-base transport.

The mammalian Rh glycoproteins belong to the solute transporter family SLC42 and include RhAG, present in red blood cells, and two non-erythroid members RhBG and RhCG that are expressed in various tissues, including kidney, liver, skin and the GI tract. The Rh proteins in the red blood cell form an "Rh complex" made up of one D-subunit, one CE-subunit and two RhAG subunits. The Rh complex has a well-known antigenic effect but also contributes to the stability of the red cell membrane.

Ion transport mechanisms linked to bicarbonate secretion in the esophageal submucosal glands.

The esophageal submucosal glands (SMG) secrete HCO(3)(-) and mucus into the esophageal lumen, where they contribute to acid clearance and epithelial protection. This study characterized the ion transport mechanisms linked to HCO(3)(-) secretion in SMG. We localized ion transporters using immunofluorescence, and we examined their expression by RT-PCR and in situ hybridization.

Role of proximal tubules in the pathogenesis of kidney disease.

The proximal tubules make up a significant portion of the kidneys; proximal tubule epithelial cells are the most populous cell type in the kidney, and carry out diverse regulatory and endocrine functions where numerous transporters are located. Under normal circumstances, more than two thirds of filtered salt and water, and all filtered bicarbonate is reabsorbed in the proximal tubule. A number of inherited and acquired acid-base and tubule disorders are linked to impaired transporters in the proximal tubule cells.

pH sensitivity of ammonium transport by Rhbg.

Rhbg is a membrane glycoprotein that is involved in NH(3)/NH(4)(+) transport. Several models have been proposed to describe Rhbg, including an electroneutral NH(4)(+)/H(+) exchanger, a uniporter, an NH(4)(+) channel, or even a gas channel. In this study, we characterized the pH sensitivity of Rhbg expressed in Xenopus oocytes.

Substrate specificity of Rhbg: ammonium and methyl ammonium transport.

Rhbg is a nonerythroid membrane glycoprotein belonging to the Rh antigen family. In the kidney, Rhbg is expressed at the basolateral membrane of intercalated cells of the distal nephron and is involved in NH4+ transport. We investigated the substrate specificity of Rhbg by comparing transport of NH3/NH4+ with that of methyl amine (hydrochloride) (MA/MA+), often used to replace NH3/NH4+, in oocytes expressing Rhbg.

The effect of tegaserod on esophageal submucosal glands bicarbonate and mucin secretion.

Tegaserod, a 5-HT4 partial agonist, was shown to reduce esophageal acid exposure in patients with gastroesophageal reflux disease; however, its mechanism of action is poorly understood. Therefore, we have examined the effect of tegaserod on luminal bicarbonate and mucin secretion in the isolated perfused pig esophagus. We also studied its role in esophageal protection using SMG-bearing pig esophagus in comparison to the rabbit esophagus, which is devoid of them.

Characterization of esophageal submucosal glands in pig tissue and cultures.

The submucosal glands (SMGs) of the pig esophagus, like the human, secrete mucin and bicarbonate, which help in luminal acid clearance and epithelial protection. The aim of this study was to characterize histochemically the esophageal SMGs and a primary culture obtained from these glands. Tissues and cultures were stained with hematoxylin and eosin, periodic acid Schiff, Alcian blue, lectins, or cytokeratins.

HCO3- secretion in the esophageal submucosal glands.

The mammalian esophagus has the capacity to secrete a HCO(3)(-) and mucin-rich fluid in the esophageal lumen. These secretions originate from the submucosal glands (SMG) and can contribute to esophageal protection against refluxed gastric acid. The cellular mechanisms by which glandular cells achieve these secretions are largely unknown.

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)(+).

Non-erythroid Rh glycoproteins: a putative new family of mammalian ammonium transporters.

The Rhesus (Rh) glycoproteins, originally described in human blood cells, are mostly recognized for their immunogenic characteristics and importance in pregnancy. The Rh proteins in the red blood cell are expressed as an "Rh complex" made up of one D-subunit, one CE-subunit and two Rh-associated glycoprotein (RhAG) subunits. In addition to its antigenic property, the Rh complex is thought to contribute to membrane stability and structure of red blood cells.

Vacuolar H(+)-ATPase in the kidney.

Proton-translocating vacuolar ATPases (H+V-ATPase) are increasingly recognized as essential components of most eukaryotic cells. This electrogenic transporter is present in the cell membranes of many differentiated cell types and in the membranes of many subcellular organelles. The primary active pump is a multi-subunit enzyme with a membrane-bound component (V0 domain) and an intracellular catalytic component (V1 domain).

Chloride transport in rabbit esophageal epithelial cells.

We investigated Cl(-) transport pathways in the apical and basolateral membranes of rabbit esophageal epithelial cells (EEC) using conventional and ion-selective microelectrodes. Intact sections of esophageal epithelium were mounted serosal or luminal side up in a modified Ussing chamber, where transepithelial potential difference and transepithelial resistance could be determined. Microelectrodes were used to measure intracellular Cl(-) activity (a), basolateral or apical membrane potentials (V(mBL) or V(mC)), and the voltage divider ratio.