title: Butyrate increases apical membrane CFTR but reduces chloride secretion in MDCK cells.
abstract: Sodium butyrate and its derivatives are useful therapeutic agents for the treatment of genetic diseases including urea cycle disorders, sickle cell disease, thalassemias, and possibly cystic fibrosis (CF). Butyrate partially restores cAMP-activated Cl(-) secretion in CF epithelial cells by stimulating DeltaF508 cystic fibrosis transmembrane conductance regulator (DeltaF508-CFTR) gene expression and increasing the amount of DeltaF508-CFTR in the plasma membrane. Because the effect of butyrate on Cl(-) secretion by renal epithelial cells has not been reported, we examined the effects of chronic butyrate treatment (15-18 h) on the function, expression, and localization of CFTR fused to the green fluorescent protein (GFP-CFTR) in stably transfected MDCK cells. We report that sodium butyrate reduced Cl(-) secretion across MDCK cells, yet increased apical membrane GFP-CFTR expression 25-fold and increased apical membrane Cl(-) currents 30-fold. Although butyrate also increased Na-K-ATPase protein expression twofold, the drug reduced the activity of the Na-K-ATPase by 55%. Our findings suggest that butyrate inhibits cAMP-stimulated Cl(-) secretion across MDCK cells in part by reducing the activity of the Na-K-ATPase.
authors.affiliation: Department of Physiology, Dartmouth Medical School, Hanover, New Hampshire 03755, USA.
authors.forename: B D
authors.initials: BD
authors.lastname: Moyer
authors.forename: D
authors.initials: D
authors.lastname: Loffing-Cueni
authors.forename: J
authors.initials: J
authors.lastname: Loffing
authors.forename: D
authors.initials: D
authors.lastname: Reynolds
authors.forename: B A
authors.initials: BA
authors.lastname: Stanton
mesh_terms: D000818:Animals; D002087:Butyrates / Q000494:pharmacology*; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism* / Q000502:physiology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism*; D004285:Dogs; D004553:Electric Conductivity; D004563:Electrochemistry; D049452:Green Fluorescent Proteins; D007202:Indicators and Reagents; D007425:Intracellular Membranes / Q000378:metabolism; D007668:Kidney / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D008164:Luminescent Proteins / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
chemical_list: D002087:Butyrates; D002352:Carrier Proteins; D002712:Chlorides; D007202:Indicators and Reagents; D008164:Luminescent Proteins; D011993:Recombinant Fusion Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D049452:Green Fluorescent Proteins; D000254:Sodium-Potassium-Exchanging ATPase