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

Abdulnour-Nakhoul S, Nakhoul HN, Kalliny MI, Gyftopoulos A, Rabon E, Doetjes R, Brown K, Nakhoul NL. Ion transport mechanisms linked to bicarbonate secretion in the esophageal submucosal glands. Am J Physiol Regul Integr Comp Physiol 301: R83-R96, 2011. First published April 6, 2011; doi:10.1152/ajpregu.00648.2010.-The esophageal submucosal glands (SMG) secrete HCO3- and mucus into the esophageal lumen, where they contribute to acid clearance and epithelial protection. This study characterized the ion transport mechanisms linked to HCO3- secretion in SMG. We localized ion transporters using immunofluorescence, and we examined their expression by RT-PCR and in situ hybridization. We measured HCO3- 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--HCO3- 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 HCO3- secretion. Genistein, an activator of CFTR, which does not increase intracellular cAMP, also stimulated HCO3- secretion, whereas glibenclamide, a Cl- channel blocker, and bumetanide, a Na+-K+-2Cl(-) blocker, decreased it. CFTRinh-172, a specific CFTR channel blocker, inhibited basal HCO3- secretion as well as stimulation of HCO3- 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.