title: SLC26A7 can function as a chloride-loading mechanism in parietal cells.
abstract: To date three potential candidates for parietal cell basolateral Cl(-) entry have been described: the highly 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS)-sensitive Cl(-)/HCO(3)(-) exchanger AE2, the HCO(3)(-) and lowly DIDS-sensitive SLC26A7 protein, and the Na(+)-2Cl(-)K(+) cotransporter (NKCC1). In this study we investigate the contribution of these pathways to secretagogue stimulated acid secretion. Individually hand-dissected rat gastric glands were microfluorimetrically monitored for Cl(-) influx and pH(i) changes. Transporter activity was determined by varying ion content and through the use of pharmacological inhibitors. Expression of SLC26A7 in rat parietal cells was shown by immunohistochemistry and Western blot. SLC26A7 was inhibited by 5-Nitro-2-(3-phenylpropyl-amino)benzoic acid (NPPB) (100 microM) in the Xenopus laevis oocyte expression system. Cl(-) influx in parietal cells was enhanced by histamine, depended partially on endogenous HCO(3)(-) synthesis and completely on extracellular Na(+). Removal and subsequent readdition of Cl(-) revealed a low and a high DIDS-sensitive HCO(3)(-) extrusion system contributing to Cl(-) uptake. At acidic pH(i), however, H(+) extrusion via the H(+),K(+)-ATPase depending on Cl(-) uptake was abolished only in the presence of 100 microM (NPPB) and at high (250 microM) DIDS concentration. There was no effect of the NKCC inhibitor bumetanide on stimulated H(+) extrusion. These results would be compatible with SLC26A7 as a Cl(-) uptake system under histamine stimulation.
authors.affiliation: Department of Surgery, Yale University School of Medicine, BML 265, 310 Cedar Street, New Haven, CT, 06520, USA.
authors.forename: Ortrud
authors.initials: O
authors.lastname: Kosiek
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Busque
authors.forename: Michael
authors.initials: M
authors.lastname: Föller
authors.forename: Nikolay
authors.initials: N
authors.lastname: Shcheynikov
authors.forename: Philipp
authors.initials: P
authors.lastname: Kirchhoff
authors.forename: Markus
authors.initials: M
authors.lastname: Bleich
authors.forename: Shmuel
authors.initials: S
authors.lastname: Muallem
authors.forename: John P
authors.initials: JP
authors.lastname: Geibel
mesh_terms: D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000818:Animals; D017920:Antiporters / Q000378:metabolism* / Q000502:physiology; D027963:Chloride-Bicarbonate Antiporters / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000166:cytology / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D066298:In Vitro Techniques; D008297:Male; D009865:Oocytes / Q000378:metabolism; D010295:Parietal Cells, Gastric / Q000378:metabolism* / Q000648:ultrastructure; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000502:physiology; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism; D064506:Solute Carrier Family 12, Member 2; D000076988:Sulfate Transporters; D014981:Xenopus
chemical_list: D017920:Antiporters; D027963:Chloride-Bicarbonate Antiporters; D002712:Chlorides; C578879:Slc12a2 protein, rat; C486744:Slc26a7 protein, rat; D028021:Sodium-Potassium-Chloride Symporters; D064506:Solute Carrier Family 12, Member 2; D000076988:Sulfate Transporters; D012964:Sodium; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid