title: Ion transport mechanisms linked to bicarbonate secretion in the esophageal submucosal glands.
abstract: 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. We measured HCO(3)(-) secretion by using pH stat and the isolated perfused esophagus. Using double labeling with Na(+)-K(+)-ATPase as a marker, we localized Na(+)-coupled bicarbonate transporter (NBCe1) and Cl(-)-HCO(3)(-) exchanger (SLC4A2/AE2) to the basolateral membrane of duct cells. Expression of cystic fibrosis transmembrane regulator channel (CFTR) was confirmed by immunofluorescence, RT-PCR, and in situ hybridization. We identified anion exchanger SLC26A6 at the ducts' luminal membrane and Na(+)-K(+)-2Cl(-) (NKCC1) at the basolateral membrane of mucous and duct cells. pH stat experiments showed that elevations in cAMP induced by forskolin or IBMX increased HCO(3)(-) secretion. Genistein, an activator of CFTR, which does not increase intracellular cAMP, also stimulated HCO(3)(-) secretion, whereas glibenclamide, a Cl(-) channel blocker, and bumetanide, a Na(+)-K(+)-2Cl(-) blocker, decreased it. CFTR(inh)-172, a specific CFTR channel blocker, inhibited basal HCO(3)(-) secretion as well as stimulation of HCO(3)(-) secretion by IBMX. This is the first report on the presence of CFTR channels in the esophagus. The role of CFTR in manifestations of esophageal disease in cystic fibrosis patients remains to be determined.
authors.affiliation: Southeast Louisiana Veterans Health Care Network, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA. solange@tulane.edu
authors.forename: Solange
authors.initials: S
authors.lastname: Abdulnour-Nakhoul
authors.forename: Hani N
authors.initials: HN
authors.lastname: Nakhoul
authors.forename: Medhat I
authors.initials: MI
authors.lastname: Kalliny
authors.forename: Alex
authors.initials: A
authors.lastname: Gyftopoulos
authors.forename: Edd
authors.initials: E
authors.lastname: Rabon
authors.forename: Rienk
authors.initials: R
authors.lastname: Doetjes
authors.forename: Karen
authors.initials: K
authors.lastname: Brown
authors.forename: Nazih L
authors.initials: NL
authors.lastname: Nakhoul
mesh_terms: D000818:Animals; D017920:Antiporters / Q000378:metabolism; D001639:Bicarbonates / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism; D004947:Esophagus / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D017136:Ion Transport / Q000502:physiology*; D023421:Models, Animal; D009092:Mucous Membrane / Q000378:metabolism; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013552:Swine
chemical_list: D017920:Antiporters; D001639:Bicarbonates; D028021:Sodium-Potassium-Chloride Symporters; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000254:Sodium-Potassium-Exchanging ATPase