title: Localization of Na+-HCO-3 cotransporter (NBC-1) variants in rat and human pancreas.
abstract: Mutations in Na(+)-HCO(3)(-) cotransporter (NBC-1) cause proximal renal tubular acidosis (pRTA) associated with ocular abnormalities. One pRTA patient had increased serum amylase, suggesting possible evidence of pancreatitis. To further delineate a link between NBC-1 inactivation and pancreatic dysfunction, immunohistochemical analysis was performed on rat and human pancreas using antibodies against kidney-type (kNBC-1) and pancreatic-type (pNBC-1) transporters. In rat pancreas, the anti-pNBC-1 antibody labeled acinar cells and both apical and basolateral membranes of medium and large duct cells. In human pancreas, on the other hand, the anti-pNBC-1 antibody did not label acinar cells, although it did label the basolateral membranes of the entire duct system. The labeling by anti-kNBC-1 antibody was detected in only a limited number of rat pancreatic duct cells. To examine the effects of pRTA-related mutations, R342S and R554H, on pNBC-1 function, we performed functional analysis and found that both mutants had reduced transport activities compared with the wild-type pNBC-1. These results indicate that pNBC-1 is the predominant variant that mediates basolateral HCO(3)(-) uptake into duct cells in both rat and human pancreas. The loss of pNBC-1 function is predicted to have significant impact on overall ductal HCO(3)(-) secretion, which could potentially lead to pancreatic dysfunction.
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, Tokyo University, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Satoh
authors.forename: Nobuo
authors.initials: N
authors.lastname: Moriyama
authors.forename: Chiaki
authors.initials: C
authors.lastname: Hara
authors.forename: Hideomi
authors.initials: H
authors.lastname: Yamada
authors.forename: Shoko
authors.initials: S
authors.lastname: Horita
authors.forename: Motoei
authors.initials: M
authors.lastname: Kunimi
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Tsukamoto
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Iso-O
authors.forename: Jun
authors.initials: J
authors.lastname: Inatomi
authors.forename: Hayato
authors.initials: H
authors.lastname: Kawakami
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kudo
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Endou
authors.forename: Takashi
authors.initials: T
authors.lastname: Igarashi
authors.forename: Atsuo
authors.initials: A
authors.lastname: Goto
authors.forename: Toshiro
authors.initials: T
authors.lastname: Fujita
authors.forename: George
authors.initials: G
authors.lastname: Seki
mesh_terms: D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D015153:Blotting, Western; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D010179:Pancreas / Q000378:metabolism*; D010182:Pancreatic Diseases / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D020033:Protein Isoforms / Q000172:deficiency / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism; D027982:Sodium-Bicarbonate Symporters / Q000172:deficiency* / Q000235:genetics
chemical_list: D001639:Bicarbonates; D020033:Protein Isoforms; D012333:RNA, Messenger; C498898:SLC4A4 protein, human; C422004:Slc4a4 protein, rat; D027982:Sodium-Bicarbonate Symporters; D012964:Sodium