title: Defective small intestinal anion secretion, dipeptide absorption, and intestinal failure in suckling NBCe1-deficient mice.
abstract: The electrogenic Na(+)HCO3 (-) cotransporter NBCe1 (Slc4a4) is strongly expressed in the basolateral enterocyte membrane in a villous/surface predominant fashion. In order to better understand its physiological function in the intestine, isolated mucosae in miniaturized Ussing chambers and microdissected intestinal villi or crypts loaded with the fluorescent pH-indicator BCECF were studied from the duodenum, jejunum, and colon of 14- to 17-days-old slc4a4-deficient (KO) and WT mice. NBCe1 was active in the basal state in all intestinal segments under study, most likely to compensate for acid loads imposed upon the enterocytes. Upregulation of other basolateral base uptake mechanism occurs, but in a segment-specific fashion. Loss of NBCe1 resulted in severely impaired Cl(-) and fluid secretory response, but not HCO3 (-) secretory response to agonist stimulation. In addition, NBCe1 was found to be active during transport processes that load the surface enterocytes with acid, such as Slc26a3 (DRA)-mediated luminal Cl(-)/HCO3 (-) exchange or PEPT1-mediated H(+)/dipeptide uptake. Possibly because of the high energy demand for hyperventilation in conjunction with the fluid secretory and nutrient absorptive defects and the relative scarcity of compensatory mechanisms, NBCe1-deficient mice developed progressive jejunal failure, worsening of metabolic acidosis, and death in the third week of life. Our data suggest that the electrogenic influx of base via NBCe1 maintains enterocyte anion homeostasis and pHi control. Its loss impairs small intestinal Cl(-) and fluid secretion as well as the neutralization of acid loads imposed on the enterocytes during nutrient and electrolyte absorption.
authors.affiliation: Department of Gastroenterology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.|Department of Gastroenterology, Tongji Hospital, Huazhong University of Science & Technology, Wuhan, People's Republic of China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Yu
authors.affiliation: Department of Gastroenterology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.|Department of Gastroenterology, Zunyi Medical College, Zunyi, China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
authors.forename: Yongjian
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Riederer
authors.affiliation: Department of Gastroenterology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.|Department of Gastrointestinal Surgery, Zunyi Medical College, Zunyi, China.
authors.forename: Taolang
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, Tongji Hospital, Huazhong University of Science & Technology, Wuhan, People's Republic of China.
authors.forename: De-An
authors.initials: DA
authors.lastname: Tian
authors.affiliation: Department of Gastroenterology, Zunyi Medical College, Zunyi, China.
authors.forename: Biguang
authors.initials: B
authors.lastname: Tuo
authors.affiliation: Department of of Molecular Genetics, University of Cincinnati, Cincinnati, OH, USA.
authors.forename: Gary
authors.initials: G
authors.lastname: Shull
authors.affiliation: Department of Gastroenterology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany. seidler.ursula@mh-hannover.de.
authors.forename: Ursula
authors.initials: U
authors.lastname: Seidler
mesh_terms: D000138:Acidosis / Q000378:metabolism; D000818:Animals; D000838:Anions / Q000378:metabolism*; D001639:Bicarbonates / Q000378:metabolism; D001692:Biological Transport / Q000502:physiology; D002712:Chlorides / Q000378:metabolism; D004151:Dipeptides / Q000378:metabolism*; D004573:Electrolytes / Q000378:metabolism; D020895:Enterocytes / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption / Q000502:physiology*; D007413:Intestinal Mucosa / Q000378:metabolism; D007421:Intestine, Small / Q000378:metabolism*; D051379:Mice; D027982:Sodium-Bicarbonate Symporters / Q000172:deficiency* / Q000378:metabolism*
chemical_list: D000838:Anions; D001639:Bicarbonates; D002712:Chlorides; D004151:Dipeptides; D004573:Electrolytes; D027982:Sodium-Bicarbonate Symporters
keywords: Anion exchange; Bicarbonate; PEPT-1; Sodium–bicarbonate cotransporter; pHi regulation