Radiation decreases murine small intestinal HCO3- secretion.

Vascular Medicine Research, Brigham and Women's Hospital, Harvard Medical School, Cambridge, Massachusetts, USA. K. Zhang
International Journal of Radiation Biology (Impact Factor: 1.84). 06/2011; 87(8):878-88. DOI: 10.3109/09553002.2011.583314
Source: PubMed

ABSTRACT While secretagogue-induced diarrhea is rich in chloride (Cl(-)) and bicarbonate (HCO(3) (-)) anions, little is known about diarrhea or its anionic composition following irradiation. We performed studies to characterize the differences between cyclic adenosine monophosphate (cAMP)-stimulated anion secretions in irradiated and non-irradiated mice.
HCO(3) (-) secretion was examined in basal, cAMP-stimulated, and irradiated jejunal tissues from BALB/c (Bagg albino) mice. The abdomens of the mice were γ-irradiated using a caesium-137 source.
Ussing-chamber experiments performed in an HCO(3)(-)-containing, Cl(-)-free solution on the bath side showed inhibition of HCO(3)(-) in irradiated mice. Non-irradiated mice exhibited bumetanide-sensitive and insensitive current, while irradiated mice displayed bumetanide-sensitive current. pH-stat experiments showed inhibition of basal and cAMP-stimulated HCO(3)(-) secretions in irradiated mice. Immunohistochemistry and Western blot analysis displayed a sodium-bicarbonate cotransporter expression in the villus and not the crypt of non-irradiated mice, while its expression and protein levels decreased in irradiated mice.
Anion secretions in irradiated mice, being primarily Cl(-) and minimally HCO(3)(-), differ from that of secretagogue-induced anion secretions. Understanding anion loss will help us correct electrolyte imbalances, while reduced HCO(3)(-) secretion in the upper-gastrointestinal tract might also have implications for irradiation-induced nausea and vomiting.


Available from: Kunzhong Zhang, Apr 18, 2015
1 Follower
  • [Show abstract] [Hide abstract]
    ABSTRACT: SGLT1-based oral rehydration solution (ORS) used in the management of acute diarrhoea does not substantially reduce stool output, despite the fact that glucose stimulates the absorption of sodium and water. To explain this phenomenon, we investigated the possibility that glucose might also stimulate anion secretion. Transepithelial electrical measurements, isotope flux measurements in Ussing chambers, fluid movement in isolated ileal sacs and electrical measurements in patch clamp studies were used to study the effect of glucose on active chloride and fluid secretion in mouse small intestinal cells and human Caco-2 cells. Confocal fluorescence laser microscopy and immunohistochemistry measured intracellular changes in calcium, SGLT1 and calcium-activated chloride channel (anoctamin 1) expression. In addition to enhancing active sodium absorption, glucose increased intracellular calcium and stimulated electrogenic chloride secretion. Calcium imaging studies showed increased intracellular calcium when intestinal cells were exposed to glucose. Niflumic acid, but not glibenclamide, inhibited glucose-stimulated chloride secretion in mouse small intestine and decreased whole-cell conductance in Caco-2 cells. In ileal intestinal sacs incubated with cholera toxin and glucose, decreased fluid secretion was seen only when the glucose-stimulated Cl secretion was blocked using niflumic acid. These observations establish that glucose not only stimulates active Na absorption, a well-established phenomenon, but also induces a Ca-activated chloride secretion. Glucose-induced chloride secretion may explain the failure of glucose-based ORS to markedly reduce stool output in acute diarrhoea. The present results have immediate potential to improve the outcome in the treatment of acute and/or chronic diarrhoeal diseases.
    AJP Cell Physiology 01/2014; 306(7). DOI:10.1152/ajpcell.00174.2013 · 3.67 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Electrolyte and nutrient absorption occur in villous epithelial cells. Radiation often results in reduced electrolyte and nutrient absorption, which leads to gastrointestinal toxicity. Therefore, the authors studied: (1) radiation-induced changes in glucose and amino acid absorption across ileal tissues and (2) the effect of amino acid mixtures on absorptive capacity. NIH Swiss mice were irradiated (0, 1, 3, 5, or 7 Gy) using a Cs source at 0.9 Gy min. Transepithelial short circuit current (Isc), dilution potential, and isotope flux determinations were made in Ussing chamber studies and correlated to plasma endotoxin and IL-1β levels. Amino acids that increased electrolyte absorption and improved mucosal barrier functions were used to create a mitigating amino acid mixture (MAAM). The MAAM was given to mice via gastric gavage; thereafter, body weight and survival were recorded. A significant decrease in basal and glucose-stimulated sodium absorption occurred after 0, 1, 3, 5, and 7 Gy irradiation. Ussing chamber studies showed that paracellular permeability increased following irradiation and that the addition of glucose resulted in a further increase in permeability. Following irradiation, certain amino acids manifested decreased absorption, whereas others were associated with increased absorption. Lysine, aspartic acid, glycine, isoleucine, threonine, tyrosine, valine, tryptophan, and serine decreased plasma endotoxins were selected for the MAAM. Mice treated with the MAAM showed increased electrolyte absorption and decreased paracellular permeability, IL-1β levels, and plasma endotoxin levels. Mice treated with MAAM also had increased weight gain and better survival following irradiation. The MAAM has immediate potential for use in mitigating radiation-induced acute gastrointestinal syndrome.
    Health physics 06/2014; 106(6):734-44. DOI:10.1097/HP.0000000000000117 · 0.77 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The mammalian Slc4 (Solute carrier 4) family of transporters is a functionally diverse group of 10 multi-spanning membrane proteins that includes three Cl-HCO3 exchangers (AE1-3), five Na(+)-coupled HCO3(-) transporters (NCBTs), and two other unusual members (AE4, BTR1). In this review, we mainly focus on the five mammalian NCBTs-NBCe1, NBCe2, NBCn1, NDCBE, and NBCn2. Each plays a specialized role in maintaining intracellular pH and, by contributing to the movement of HCO3(-) across epithelia, in maintaining whole-body pH and otherwise contributing to epithelial transport. Disruptions involving NCBT genes are linked to blindness, deafness, proximal renal tubular acidosis, mental retardation, and epilepsy. We also review AE1-3, AE4, and BTR1, addressing their relevance to the study of NCBTs. This review draws together recent advances in our understanding of the phylogenetic origins and physiological relevance of NCBTs and their progenitors. Underlying these advances is progress in such diverse disciplines as physiology, molecular biology, genetics, immunocytochemistry, proteomics, and structural biology. This review highlights the key similarities and differences between individual NCBTs and the genes that encode them and also clarifies the sometimes confusing NCBT nomenclature.
    Physiological Reviews 04/2013; 93(2):803-959. DOI:10.1152/physrev.00023.2012 · 29.04 Impact Factor