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Bicarbonate secretion

Junwei Huang, Dusik Kim, Jiajie Shan, Asmahan Abu-Arish, Yishan Luo, John W Hanrahan
Bicarbonate plays an important role in airway host defense, however, its transport mechanisms remain uncertain. Here we examined the relative contributions of the anion channel CFTR (cystic fibrosis transmembrane conductance regulator, ABCC7) and the anion exchanger pendrin (SLC26A4) to HCO3 - secretion by the human airway cell line Calu-3. Pendrin and CFTR were both detected in parental Calu-3 cells, although mRNA and protein expression appeared higher for CFTR than for pendrin. Targeting pendrin transcripts with lentiviral shRNA reduced pendrin detection by immunofluorescence staining but did not alter the rates of HCO3 - or fluid secretion, HCO3 - transport under pH-stat conditions, or net HCO3 - flux across basolaterally permeabilized monolayers...
March 2018: Physiological Reports
Junbo Zhu, Yongtao Yu, Hongbo Li, Fenshuang Zheng, Ruyun Lin, Chun'ai Yang
OBJECTIVE: To explore the effect of sucralfate on cytokines in rats with paraquat (PQ) poisoning. METHODS: Seventy-two healthy male Sprague-Dawley (SD) rats were randomly divided into PQ model group, sodium bicarbonate intervention group (SB group) and sucralfate suspension gel group (LTL group), with 24 rats in each group. The rat model of PQ poisoning was reproduced by one-time intragastric administration of PQ solution 25 mg/kg. The rats in SB group and LTL group were intragastricly administrated with 5 mL×kg-1 ×d-1 of 100 g/L sodium bicarbonate or 200 g/L sucralfate at 2 hours after exposing to PQ, and the rats in PQ model group were given the same amount of sterile saline...
March 2018: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
Yunxia O'Malley, Pavana G Rotti, Ian M Thornell, Oriana G Vanegas Calderón, Christopher Febres-Aldana, Katelin Durham, Jianrong Yao, Xiaopeng Li, Zheng Zhu, Andrew W Norris, Joseph Zabner, John F Engelhardt, Aliye Uc
Pancreatic ductular epithelial cells comprise the majority of duct cells in pancreas, control cystic fibrosis transmembrane conductance regulator (CFTR)-dependent bicarbonate [HCO3 - ] secretion, but are difficult to grow as a polarized monolayer. Using NIH-3T3-J2 fibroblast feeder cells and a Rho-associated kinase inhibitor, we produced well-differentiated and polarized porcine pancreatic ductular epithelial cells. Cells grown on semipermeable filters at air-liquid interface (ALI) developed typical epithelial cell morphology and stable transepithelial resistance (TER), expressed epithelial cell markers (zona occludens-1 and beta catenin), duct cell markers (SOX-9 and CFTR), but no acinar (amylase) or islet cell (chromogranin) markers...
March 8, 2018: Journal of Applied Physiology
Miriam Zacchia, Giovanna Capolongo, Luca Rinaldi, Giovambattista Capasso
The thick ascending limb (TAL) of Henle's loop is a crucial segment for many tasks of the nephron. Indeed, the TAL is not only a mainstay for reabsorption of sodium (Na+ ), potassium (K+ ), and divalent cations such as calcium (Ca2+ ) and magnesium (Mg2+ ) from the luminal fluid, but also has an important role in urine concentration, overall acid-base homeostasis, and ammonia cycle. Transcellular Na+ transport along the TAL is a prerequisite for Na+ , K+ , Ca2+ , Mg2+ homeostasis, and water reabsorption, the latter through its contribution in the generation of the cortico-medullar osmotic gradient...
2018: International Journal of Nephrology and Renovascular Disease
Hyun-Wook Lee, Gunars Osis, Autumn N Harris, Lijuan Fang, Michael F Romero, Mary E Handlogten, Jill W Verlander, I David Weiner
Renal ammonia metabolism is the primary mechanism through which the kidneys maintain acid-base homeostasis, but the molecular mechanisms regulating renal ammonia generation are unclear. In these studies, we evaluated the role of the proximal tubule basolateral plasma membrane electrogenic sodium bicarbonate cotransporter 1 variant A (NBCe1-A) in this process. Deletion of the NBCe1-A gene caused severe spontaneous metabolic acidosis in mice. Despite this metabolic acidosis, which normally causes a dramatic increase in ammonia excretion, absolute urinary ammonia concentration was unaltered...
February 26, 2018: Journal of the American Society of Nephrology: JASN
Mujan Varasteh Kia, Sharon Barone, Alicia A McDonough, Kamyar Zahedi, Jie Xu, Manoocher Soleimani
BACKGROUND/AIMS: Patients with cystic fibrosis (CF) are prone to the development of metabolic alkalosis; however, the pathogenesis of this life threatening derangement remains unknown. We hypothesized that altered acid base transport machinery in the kidney collecting duct underlies the mechanism of impaired bicarbonate elimination in the CF kidney. METHODS: Balance studies in metabolic cages were performed in WT and CFTR knockout (CF) mice with the intestinal rescue in response to bicarbonate loading or salt restriction, and the expression levels and cellular distribution of acid base and electrolyte transporters in the proximal tubule, collecting duct and small intestine were examined by western blots, northern blots and/or immunofluorescence labeling...
February 21, 2018: Cellular Physiology and Biochemistry
Sergio Trillo-Muyo, Harriet E Nilsson, Christian V Recktenwald, Anna Ermund, Caroline Ridley, Lauren N Meiss, Andrea Bahr, Nikolai Klymiuk, Jeffrey J Wine, Philip J Koeck, David J Thornton, Hans Hebert, Gunnar C Hansson
Most MUC5B mucin polymers in the upper airways of humans and pigs are produced by submucosal glands. MUC5B forms N-terminal covalent dimers, which are further packed into larger assemblies because of low pH and high Ca2+ in the secretory granule of the mucin-producing cell. We purified the recombinant MUC5B N-terminal covalent dimer and used single-particle electron microscopy to study its structure under intracellular conditions. We found that at intragranular pH, the dimeric MUC5B organized into head-to-head noncovalent tetramers where the von Willebrand D1-D2 domains hooked into each other...
February 13, 2018: Journal of Biological Chemistry
Xin Yang, Guorong Wen, Biguang Tuo, Fenglian Zhang, Hanxing Wan, Jialin He, Shiming Yang, Hui Dong
Background and Purpose: Although Ca2+ signaling may stimulate small intestinal ion secretion, little is known about its critical role and the molecular mechanisms of Ca2+-mediated biological action. Key Results: Activation of muscarinic receptors by carbachol(CCh) stimulated mouse duodenal Isc, which was significantly inhibited in Ca2+-free serosal solution and by several selective store-operated Ca2+ channels(SOC) blockers added to the serosal side of duodenal tissues...
January 9, 2018: Oncotarget
Qin Li, Amal Dutta, Charles Kresge, Abhijit Bugde, Andrew P Feranchak
Bile acids stimulate a bicarbonate-rich choleresis in part through effects on cholangiocytes. As Cl- channels in the apical membrane of cholangiocytes provide the driving force for secretion and TMEM16A has been identified as the Ca2+ -activated Cl- channel in the apical membrane of cholangiocytes (1), the aim of the present study was to determine if TMEM16A is the target of bile acid-stimulated Cl- secretion and to identify the regulatory pathway involved. In these studies of mouse, rat, and human biliary epithelium exposure to Ursodeoxycholic acid (UDCA) or Tauroursodeoxycholic acid (TUDCA) rapidly increased the rate of exocytosis, ATP release, [Ca2+ ]i , membrane Cl- permeability, and transepithelial secretion...
January 23, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
James F Collawn, Rafal Bartoszewski, Ahmad Lazrak, Sadis Matalon
The airway surface liquid (ASL) coats the lining of the airways and allows for efficient cilial movement and therefore effective mucociliary transport. Cell surface channels regulate the hydration status of the ASL and the two critical channels in the process are the cystic fibrosis transmembrane conductance regulator (CFTR) and the amiloride-sensitive epithelial sodium channel (ENaC). In cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) there is loss of CFTR function or compromised CFTR function in chronic bronchitis, respectively...
January 4, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
Susan E Birket, Joy M Davis, Courtney M Fernandez, Katherine L Tuggle, Ashley M Oden, Kengyeh K Chu, Guillermo J Tearney, Michelle V Fanucchi, Eric J Sorscher, Steven M Rowe
The mechanisms underlying the development and natural progression of the airway mucus defect in cystic fibrosis (CF) remain largely unclear. New animal models of CF, coupled with imaging using micro-optical coherence tomography, can lead to insights regarding these questions. The Cftr-/- (KO) rat allows for longitudinal examination of the development and progression of airway mucus abnormalities. The KO rat exhibits decreased periciliary depth, hyperacidic pH, and increased mucus solid content percentage; however, the transport rates and viscoelastic properties of the mucus are unaffected until the KO rat ages...
January 11, 2018: JCI Insight
Alix P M Matton, Laura C Burlage, Rianne van Rijn, Yvonne de Vries, Shanice A Karangwa, Maarten W Nijsten, Annette S H Gouw, Janneke Wiersema-Buist, Jelle Adelmeijer, Andrie C Westerkamp, Ton Lisman, Robert J Porte
BACKGROUND: Normothermic machine perfusion (NMP) enables viability assessment of donor livers prior to transplantation. NMP is frequently performed using human blood products including red blood cells (RBC) and fresh frozen plasma (FFP). Our aim was to examine the efficacy of a novel machine perfusion solution based on polymerized bovine hemoglobin HBOC-201. METHODS: Twenty-four livers declined for transplantation were transported using static cold storage. Upon arrival, livers underwent NMP for 6 hours using pressure-controlled portal and arterial perfusion...
December 27, 2017: Liver Transplantation
Sonia Del Prete, Daniela Vullo, Natacha Caminiti-Segonds, Didier Zoccola, Sylvie Tambutté, Claudiu T Supuran, Clemente Capasso
CruCA4 is a secreted isoform of the α-carbonic anhydrase (CA, EC family, which has been identified in the octocoral Corallium rubrum. This enzyme is involved in the calcification process leading to the formation of the coral calcium carbonate skeleton. We report here experiments performed on the recombinant CruCA4 with the technique of protonography that can be used to detect in a simple way the enzyme activity. We have also investigated the inhibition profile of CruCA4 with one major class of CA inhibitors, the inorganic anions...
February 2018: Bioorganic Chemistry
Aswini Kumar Pujahari
Most of pain-relieving agents in chronic pancreatitis are nonspecific and unpredictable. Omeprazole induces hypergastrinemia due to reduced gastric acidity. Raised serum gastrin, in turn, modulates to reduce secretin level. Secretin is responsible for secretion of almost 80 % bicarbonate-rich pancreatic juice from the ductular epithelium without affecting enzyme output. It is a prospective randomized study in patients with CT-confirmed chronic pancreatitis. The control group got the standard care and 60 mg of omeprazole twice daily was added to the test group...
December 2017: Indian Journal of Surgery
Jose Antonio Uranga, Marta Castro, Raquel Abalo
Guanylate cyclase C (GC-C) receptor is a transmembrane receptor, predominantly expressed in intestinal epithelial cells, that plays a main role in homeostasis and function of the digestive tract. The endogenous ligands for this receptor are the paracrine hormones uroguanylin and guanylin. The heat-stable enterotoxin, produced by enterotoxigenic bacteria, is also a natural ligand of this receptor. Upon ligand binding, GC-C receptors increase the second messenger cyclic guanosine monophosphate (cGMP) levels, regulating a variety of key cell-type specific processes such as chloride and bicarbonate secretion (which increases luminal fluid and intestinal motility), epithelial cell growth, regulation of intestinal barrier integrity and visceral sensitivity...
December 5, 2017: Current Medicinal Chemistry
Theodossis S Papavramidis, Olympia Anastasiou, Ioannis Pliakos, George Kotsovolis, Stavros Panidis, Antonios Michalopoulos
Background Thyroidectomy impairs parathyroid function, even if it does not necessarily lead to postoperative clinical hypocalcaemia. This study is prospective and evaluates the PTH function in non-clinically symptomatic patients after total thyroidectomy performed by two different techniques. Materials and Methods Prospective randomized clinical trial including 269 patients undergoing classic (group A) or harmonic scalpel (group B) total thyroidectomy. Preoperatively and at 48 hours biochemical analysis was performed...
November 16, 2017: Endocrine Practice
Miroslav Vujasinovic, Roberto Valente, Anders Thorell, Wiktor Rutkowski, Stephan L Haas, Urban Arnelo, Lena Martin, J-Matthias Löhr
Morbid obesity is a lifelong disease, and all patients require complementary follow-up including nutritional surveillance by a multidisciplinary team after bariatric procedures. Pancreatic exocrine insufficiency (PEI) refers to an insufficient secretion of pancreatic enzymes and/or sodium bicarbonate. PEI is a known multifactorial complication after upper gastrointestinal surgery, and might constitute an important clinical problem due to the large number of bariatric surgical procedures in the world. Symptoms of PEI often overlap with sequelae of gastric bypass, making the diagnosis difficult...
November 13, 2017: Nutrients
Qiubing Chen, Xiaoying Si, Lijun Ma, Panpan Ma, Meili Hou, Shuang Bai, Xiaoshuai Wu, Ying Wan, Bo Xiao, Didier Merlin
Oral drug delivery has been considered as a promising strategy for ulcerative colitis (UC) therapy. Here, an emulsion solvent evaporation technique was employed to prepare non-porous curcumin (CUR)-loaded polymeric nanoparticles (NPs) and porous CUR-loaded polymeric NPs in the absence or presence of ammonium bicarbonate. The resultant CUR-loaded NPs (non-porous NPs and porous NPs) had a desirable mean particle size of around 260 nm with a narrow size distribution, a uniform pore size distribution, slightly negative-charged surface, high encapsulation efficiency and controlled drug release capacity...
August 7, 2017: Journal of Materials Chemistry. B, Materials for Biology and Medicine
Roberta Benedetto, Jiraporn Ousingsawat, Podchanart Wanitchakool, Yong Zhang, Michael J Holtzman, Margarida Amaral, Jason R Rock, Rainer Schreiber, Karl Kunzelmann
Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is the secretory chloride/bicarbonate channel in airways and intestine that is activated through ATP binding and phosphorylation by protein kinase A, but fails to operate in cystic fibrosis (CF). TMEM16A (also known as anoctamin 1, ANO1) is thought to function as the Ca(2+) activated secretory chloride channel independent of CFTR. Here we report that tissue specific knockout of the TMEM16A gene in mouse intestine and airways not only eliminates Ca(2+)-activated Cl(-) currents, but unexpectedly also abrogates CFTR-mediated Cl(-) secretion and completely abolishes cAMP-activated whole cell currents...
September 29, 2017: Scientific Reports
Jung-Chin Chang, Simei Go, Arthur J Verhoeven, Ulrich Beuers, Ronald P J Oude Elferink
Primary biliary cholangitis (PBC) is a chronic fibrosing cholangiopathy characterized by an autoimmune stereotype and defective biliary bicarbonate secretion due to down-regulation of anion exchanger 2 (AE2). Despite the autoimmune features, immunosuppressants are ineffective while two bile acid-based therapies (ursodeoxycholic acid and obeticholic acid) have been shown to improve biochemical and histological features of cholestasis and long-term prognosis. However, the etiology and pathogenesis of PBC is largely unknown...
September 26, 2017: Biochimica et Biophysica Acta
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