title: Regulated traffic of anion transporters in mammalian Brunner's glands: a role for water and fluid transport.
abstract: The Brunner's glands of the proximal duodenum exert barrier functions through secretion of glycoproteins and antimicrobial peptides. However, ion transporter localization, function, and regulation in the glands are less clear. Mapping the subcellular distribution of transporters is an important step toward elucidating trafficking mechanisms of fluid transport in the gland. The present study examined 1) changes in the distribution of intestinal anion transporters and the aquaporin 5 (AQP5) water channel in rat Brunner's glands following second messenger activation and 2) anion transporter distribution in Brunner's glands from healthy and disease-affected human tissues. Cystic fibrosis transmembrane conductance regulator (CFTR), AQP5, sodium-potassium-coupled chloride cotransporter 1 (NKCC1), sodium-bicarbonate cotransporter (NBCe1), and the proton pump vacuolar ATPase (V-ATPase) were localized to distinct membrane domains and in endosomes at steady state. Carbachol and cAMP redistributed CFTR to the apical membrane. cAMP-dependent recruitment of CFTR to the apical membrane was accompanied by recruitment of AQP5 that was reversed by a PKA inhibitor. cAMP also induced apical trafficking of V-ATPase and redistribution of NKCC1 and NBCe1 to the basolateral membranes. The steady-state distribution of AQP5, CFTR, NBCe1, NKCC1, and V-ATPase in human Brunner's glands from healthy controls, cystic fibrosis, and celiac disease resembled that of rat; however, the distribution profiles were markedly attenuated in the disease-affected duodenum. These data support functional transport of chloride, bicarbonate, water, and protons by second messenger-regulated traffic in mammalian Brunner's glands under physiological and pathophysiological conditions.
authors.affiliation: Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Collaco
authors.forename: Robert L
authors.initials: RL
authors.lastname: Jakab
authors.forename: Nadia E
authors.initials: NE
authors.lastname: Hoekstra
authors.forename: Kisha A
authors.initials: KA
authors.lastname: Mitchell
authors.forename: Amos
authors.initials: A
authors.lastname: Brooks
authors.forename: Nadia A
authors.initials: NA
authors.lastname: Ameen
mesh_terms: D000818:Animals; D027321:Anion Transport Proteins / Q000032:analysis / Q000378:metabolism*; D051402:Aquaporin 5 / Q000032:analysis / Q000378:metabolism; D001639:Bicarbonates / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D002011:Brunner Glands / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D002217:Carbachol / Q000494:pharmacology; D002446:Celiac Disease / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D000242:Cyclic AMP / Q000494:pharmacology; D003550:Cystic Fibrosis / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000032:analysis; D004386:Duodenum / Q000737:chemistry / Q000473:pathology; D006801:Humans; D008297:Male; D011522:Protons; D051381:Rats; D017207:Rats, Sprague-Dawley; D015290:Second Messenger Systems / Q000502:physiology; D025262:Vacuolar Proton-Translocating ATPases / Q000032:analysis; D014867:Water / Q000378:metabolism*
chemical_list: D027321:Anion Transport Proteins; D051402:Aquaporin 5; D001639:Bicarbonates; C505032:CFTR protein, human; C579654:CFTR protein, rat; D002712:Chlorides; D011522:Protons; D014867:Water; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D002217:Carbachol; D000242:Cyclic AMP; D025262:Vacuolar Proton-Translocating ATPases
keywords: Brunner's glands; ion transporters; regulated traffic