title: The ethanol-induced stimulation of rat duodenal mucosal bicarbonate secretion in vivo is critically dependent on luminal Cl-.
abstract: Alcohol may induce metabolic and functional changes in gastrointestinal epithelial cells, contributing to impaired mucosal barrier function. Duodenal mucosal bicarbonate secretion (DBS) is a primary epithelial defense against gastric acid and also has an important function in maintaining the homeostasis of the juxtamucosal microenvironment. The aim in this study was to investigate the effects of the luminal perfusion of moderate concentrations of ethanol in vivo on epithelial DBS, fluid secretion and paracellular permeability. Under thiobarbiturate anesthesia, a ∼30-mm segment of the proximal duodenum with an intact blood supply was perfused in situ in rats. The effects on DBS, duodenal transepithelial net fluid flux and the blood-to-lumen clearance of 51Cr-EDTA were investigated. Perfusing the duodenum with isotonic solutions of 10% or 15% ethanol-by-volume for 30 min increased DBS in a concentration-dependent manner, while the net fluid flux did not change. Pre-treatment with the CFTR inhibitor CFTRinh172 (i.p. or i.v.) did not change the secretory response to ethanol, while removing Cl- from the luminal perfusate abolished the ethanol-induced increase in DBS. The administration of hexamethonium (i.v.) but not capsazepine significantly reduced the basal net fluid flux and the ethanol-induced increase in DBS. Perfusing the duodenum with a combination of 1.0 mM HCl and 15% ethanol induced significantly greater increases in DBS than 15% ethanol or 1.0 mM HCl alone but did not influence fluid flux. Our data demonstrate that ethanol induces increases in DBS through a mechanism that is critically dependent on luminal Cl- and partly dependent on enteric neural pathways involving nicotinic receptors. Ethanol and HCl appears to stimulate DBS via the activation of different bicarbonate transporting mechanisms.
authors.affiliation: Division of Gastrointestinal Physiology, Department of Neuroscience, Uppsala University, Uppsala, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Sommansson
authors.affiliation: Division of Gastrointestinal Physiology, Department of Neuroscience, Uppsala University, Uppsala, Sweden.
authors.forename: Wan Salman
authors.initials: WS
authors.lastname: Wan Saudi
authors.affiliation: Division of Gastrointestinal Physiology, Department of Neuroscience, Uppsala University, Uppsala, Sweden.
authors.forename: Olof
authors.initials: O
authors.lastname: Nylander
authors.affiliation: Division of Gastrointestinal Physiology, Department of Neuroscience, Uppsala University, Uppsala, Sweden.
authors.forename: Markus
authors.initials: M
authors.lastname: Sjöblom
mesh_terms: D000818:Animals; D027321:Anion Transport Proteins / Q000378:metabolism; D017920:Antiporters / Q000378:metabolism; D001639:Bicarbonates / Q000378:metabolism*; D001826:Body Fluids / Q000378:metabolism; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D002713:Chlorine / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000037:antagonists & inhibitors; D004386:Duodenum / Q000378:metabolism*; D000431:Ethanol / Q000009:adverse effects / Q000494:pharmacology*; D005744:Gastric Acid / Q000378:metabolism; D018738:Hexamethonium / Q000494:pharmacology; D006851:Hydrochloric Acid / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D018733:Nicotinic Antagonists / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000378:metabolism; D000076988:Sulfate Transporters
chemical_list: D027321:Anion Transport Proteins; D017920:Antiporters; D001639:Bicarbonates; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; C466903:Slc26a1 protein, mouse; D000076988:Sulfate Transporters; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D018738:Hexamethonium; D000431:Ethanol; D002713:Chlorine; C071423:capsazepine; D006851:Hydrochloric Acid; D002211:Capsaicin